Immunological Abnormalities in Asymptomatic Homosexual Men: Correlation with Antibody to HTLV-III and Sequential Changes over Two Years

A prospective study on 100 homosexual male volunteers was designedto examine immunological function in relation to sexual activityand infection with the human T cell lymphotropic virus TypeIII (HTLV-III). Complete data were available for 71 men. Ina comparison with 100 age matched heterosexual men, the studygroup of 100 men had a significantly higher mean serum IgG level(12.1±SD 2.7 g/l vs. 10.9±2.4 g/l, p<0.01)and a significantly lower mean number of CD4 (T4) cells (845±310x10^–6/lvs. 1128±375;p<0.01). For the study group, seropositivityfor anti-HTLV-III was present initially in 22 per cent and wasassociated with a higher mean level of serum IgG and lower meannumber of CD4 cells. Among seropositive homosexual men a lowCD4/8 ratio was attributable to low numbers of CD4 cells inthose without lymphadenopathy and to high numbers of CD8 cellsin those with lymphadenopathy. For the seronegative homosexualmen, a low CD4/8 ratio as a result of an increased CD8 cellcount was present in 12 of 60, and was associated with numeroussexual partners and semen culture positive for cytomegalovirus.In two seropositive subjects a low CD4/8 ratio due to a decreasein the CD4 cell count was predictive of the development of AIDSby some two years. For the 71 men with complete data over twoyears, indices of cell-mediated immunity, including mean countsof CD4 cells, the CD4/8 ratio, and score for recall of cutaneousdelayed type hypersensitivity increased during the first yearbut not during the second year in both seropositive and seronegativesubjects. These increases occurred in association with changesin sexual practices and activity, but could not be attributedto any one particular factor.     

Immunological abnormalities in human immunodeficiency virus (HIV)-infected asymptomatic homosexual men. HIV affects the immune system before CD4+ T helper cell depletion occurs.

To investigate the effect of persistent HIV infection on the immune system, we studied leukocyte functions in 14 asymptomatic homosexual men (CDC group II/III) who were at least two years seropositive, but who still had normal numbers of circulating CD4+ T cells. Compared with age-matched heterosexual men and HIV-negative homosexual men, the CD4+ and CD8+ T cells from seropositive men showed decreased proliferation to anti-CD3 monoclonal antibody and decreased CD4+ T-helper activity on PWM-driven differentiation of normal donor B cells. Monocytes of HIV-infected homosexual men showed decreased accessory function on normal T cell proliferation induced by CD3 monoclonal antibody. The most striking defect in leukocyte functional activities was observed in the B cells of HIV-infected men. B cells of 13 out of 14 seropositive men failed to produce Ig in response to PWM in the presence of adequate allogeneic T-helper activity. These findings suggest that HIV induces severe immunological abnormalities in T cells, B cells, and antigen-presenting cells early in infection before CD4+ T cell numbers start to decline. Impaired immunological function in subclinically HIV-infected patients may have clinical implications for vaccination strategies, in particular the use of live vaccines in groups with a high prevalence of HIV seropositivity.     

The effect of cigarette smoking on lymphocyte subsets and progression to AIDS in a cohort of homosexual men.

We investigated the effect of cigarette smoking on the percentage of CD4 and CD8 cells (CD4%, CD8%) within a prospective study of homosexual men in Vancouver, Canada and compared progression rates to AIDS among seroincident smokers and non-smokers. Serial measurements of CD4% and CD8% obtained from four annual visits were available for 299 men and were compared with respect to smoking status and serologic group. CD4% was significantly elevated (p less than 0.025) and CD8% was significantly lower (p less than 0.002) in seronegative smokers compared to non-smokers. However, no effect of smoking was observed in the seropositive group for either of these variables. In a prospective analysis of 122 seroincident subjects, we failed to find a significant association between smoking and progression to AIDS (p = 0.829) or Pneumocystis carinii pneumonia (p = 0.894). At 72 months, cumulative AIDS progression was 29.1% in seroincident smokers compared to 25.2% in seroincident non-smokers. These data suggest that in the absence of HIV, smoking is associated with higher CD4% and lower CD8% but these effects are not present in seropositive subjects with longer durations of infection. Cigarette smoking does not appear to be associated with an altered rate of progression to AIDS.     

Neopterin estimation compared with the ratio of T-cell subpopulations in persons infected with human immunodeficiency virus-1

We measured neopterin, a biochemical indicator for the activation of cell-mediated immune reactions, in urines from 105 individuals at risk of infection with human immunodeficiency virus-1 (HIV-1), 83 of whom were seropositive for antibody to HIV-1. We compared absolute numbers of T-cell subsets (CD4+ helper/inducer T-cells, CD8+ suppressor/cytotoxic T-cells), and the ratio of CD4+ T-cells to CD8+ T-cells with the urinary neopterin concentrations. Concentrations of neopterin in urine were inversely correlated with absolute numbers of CD4+ T-cells and with CD4+/CD8+ ratios in anti-HIV-1 seropositive subjects but not in those seronegative. Various statistical comparisons of the data further demonstrated that neopterin concentrations showed larger differences between anti-HIV-1 seronegative and seropositive subjects than absolute numbers of CD4+ T-cells or CD4+/CD8+ ratios. These results seem to indicate that neopterin concentrations increase earlier in the course of HIV-1 infection, before effects on T-cell subpopulations are detectable, and may further support the suggestion that neopterin measurement could be of use for monitoring infected subjects or predicting the progression of disease.     

Screening of blood donors for idiopathic CD4+ T-lymphocytopenia

BACKGROUND: The recent recognition of idiopathic CD4+ T-lymphocytopenia (ICL) had led to concern that an unknown immunodeficiency virus may be transmissible by transfusion. STUDY DESIGN AND METHODS: To evaluate the prevalence and significance of low CD4+ values among blood donors, CD4+ data on 2030 blood donors who were negative for antibody to human immunodeficiency virus type 1 (HIV-1) were compiled. Those with CD4+ values below ICL cutoffs (< 300 CD4+ T cells/microL, or < 20% CD4+ T cells) were recalled for follow-up investigations. Serial CD4+ data on 55 homosexual men who seroconverted during prospective follow-up and data on 139 anti-HIV-1-positive blood donors initially evaluated in 1986 were reviewed as well. RESULTS: Five seronegative donors (0.25%) had absolute CD4+ counts < 300 cells per microL and/or < 20 percent. On follow-up, all five donors had immunologic findings within normal ranges, lacked HIV risk factors, and tested negative for HIV types 1 and 2 and human T-lymphotropic virus type I and II infections by antibody and polymerase chain reaction assays. Four of five donors reported transient illness shortly after their low CD4+ count donations. The median interval from HIV-1 seroconversion to an initial CD4+ value below ICL CD4+ cutoffs was 63 months for infected homosexual men. Of 139 HIV-1-infected blood donors studied 1 to 2 years after seropositive donations, 34 (24%) had CD4+ counts < 300 cells per microL and/or < 20 percent. CONCLUSION: Low CD4+ counts are rare among anti- HIV-1-negative volunteer blood donors and are generally associated with transient illnesses. If any unknown virus progresses similarly to HIV- 1, CD4+ count donor screening would be a poor surrogate for its detection.     

Serum β2-microglobulin in intravenous drug users and its correlation with human immunodeficiency virus infectionin intravenous drug users and its correlation with human immunodeficiency virus infection

Summary High levels of serum β₂-microglobulin have been associated with human immunodeficiency virus infection and β₂-microglobulin has been used with other serological and immunological markers for monitoring disease progression. The usefulness of β₂-microglobulin as a prognostic marker during human immunodeficiency virus infection has been demonstrated in homosexual men and hemophiliacs; few and contradictory data have been reported in intravenous drug users. We have evaluated a cohort of 160 intravenous drug users (81 seronegative and 79 seropositive for human immunodeficiency virus infection) with normal renal function to assess whether serum β₂-microglobulin could be used as a serological marker for monitoring infection; 78 healthy subjects were used as controls. Of 79 seropositive drug users, 54 were asymptomatic or had persistent generalized lymphoadenopathy the remaining 25 had the acquired immunodeficiency syndrome. Seropositive patients were tested for CD4⁺ lymphocyte number, p24 antigen and anti-p24 antibodies. A significant statistical difference was found in mean serum β₂-microglobulin levels between seronegative and seropositive drug users. Moreover, higher levels of β₂-microglobulin were observed in acquired immunodeficiency syndrome patients compared with asymptomatic or patients with persistent lymphadenopathy. A significant relationship was also observed between increased concentration of β₂-microglobulin and the serological and immunological markers which indicate human immunodeficiency virus disease progression.     

Immunoregulatory subsets of the T helper and T suppressor cell populations in homosexual men with chronic unexplained lymphadenopathy

Unexplained, generalized lymphadenopathy in homosexual men, which can be a prodrome to the acquired immunodeficiency syndrome, is associated with impaired cell-mediated immunity, a low ratio of T helper-inducer to T suppressor-cytotoxic cells (defined by the T4 and T8 monoclonal antibodies), and hypergammaglobulinemia. We performed double-marker studies on T cells by using a panel of monoclonal antibodies (Ia, T17, TQ1, and Leu-8), which reportedly detect activation or functional subsets of the T4 and T8 T cell populations. The T4:TQ1- or T4:Leu-8- subset, which is the major helper subset for B cell responses, is normally represented in lymphadenopathy patients. A depression in the reciprocal subset, T4:TQ1+ or T4:Leu-8+, accounts for the T4 T cell defect. Similarly, the TQ1 and Leu-8 markers delineate the abnormality of T8 T cells: the T8:TQ1- or T8:Leu-8- subset is elevated, whereas the T8:TQ1+ or T8:Leu-8+ subset is normally represented. We found no evidence of excessive activation of T4 T cells by using the T17 or Ia monoclonal antibodies. We did find an overall increase in Ia-positive T cells; however, this was due to increased T8:Ia+ cells. In functional studies, immunoglobulin production induced by pokeweed was subnormal. Most lymphadenopathy patients had normal T helper cell function when combined with normal B cells. The dampened pokeweed responses could be partially explained by depression of the T4:TQ1+ (or T4:Leu-8+) subset (which has minor help-associated function) and/or greater than expected suppression. However, subnormal pokeweed responses could not be totally explained by immunoregulatory T cell abnormalities because we also found an intrinsic defect in the B cell responses of lymphadenopathy patients.     

American blood donors seropositive for human T-lymphotropic virus types I/II exhibit normal lymphocyte subsets

Recent reports have demonstrated that some lymphocyte subsets are abnormal in Japanese blood donors who are seropositive for human T-lymphotropic virus type I (HTLV-I). To determine if similar changes characterize American blood donors who are seropositive for HTLV-I/II, lymphocyte subsets were measured in 42 HTLV-seropositive and 42 HTLV-seronegative blood donors. The seronegative individuals were matched by age, race, and gender to the seropositive individuals. Peripheral blood mononuclear cells were treated with a panel of 12 monoclonal antibody pairs and then analyzed by two-color flow cytometry. No significant differences were observed between the seropositive and seronegative groups with respect to the absolute number of circulating lymphocytes or the percentages of lymphocytes belonging to the subsets assessed. These subsets included B, T, CD4, and CD8 cells and subpopulations of CD4 and CD8 cells defined by the coexpression of markers that appear (CD25, HLA-DR, CD38) or disappear (Leu 8, CD45RA) after activation. These findings indicate that HTLV-seropositive persons in the American blood donor pool do not exhibit the lymphocyte subset alterations reported for HTLV-I-seropositive blood donors in Japan.     

Neopterin as a predictive marker for disease progression in human immunodeficiency virus type 1 infection

We assessed the value of urinary neopterin concentrations for prognosis of disease progression in HIV-1-infected patients. Sixty-eight anti-HIV-1 seropositive homosexuals with lymphadenopathy syndrome were tested for urinary neopterin and T-cell subset counts in 1982-83, and the incidence rate at which they developed acquired immunodeficiency syndrome (AIDS) between then and May 1988 was evaluated. Overall, 21 of 68 (30.9%) cases progressed to AIDS, with a yearly progression rate of 4-9%. The predictive value of urinary neopterin concentrations was higher (P = 0.0042) than that of CD4+ T-cell counts (P = 0.015) or the CD4+/CD8+ T-cell ratio (P = 0.022). Counts of CD8+ T-cells failed to show predictive significance (P = 0.29). Similarly, multivariate-regression analysis indicated that neopterin concentrations and CD4+ T-cell numbers were significant copredictors. Produced by human macrophages activated by interferon gamma, neopterin is thus a marker of macrophage activation via T cells. We conclude that these data demonstrate a correlation between the amount of T-cell-macrophage activation, as measured by urinary neopterin concentrations, and the progression of the disease.     

Epidemiologic background and long-term course of disease in human immunodeficiency virus type 1-infected blood donors identified before routine laboratory screening. Transfusion Safety Study Group

BACKGROUND: The long-term course of human immunodeficiency virus type 1 (HIV-1)-related disease among seropositive blood donors has not been described. The enrollment and epidemiologic background of HIV-1- infected donors in the Transfusion Safety Study and their immunologic and clinical progression are described. STUDY DESIGN AND METHODS: Through the testing of approximately 200,000 sera from donations made in late 1984 and early 1985, 146 anti-HIV-1-positive donors and 151 uninfected matched donors were enrolled. These two cohorts were followed with 6-month interval histories and laboratory testing. RESULTS: Seropositive donors detected before the institution of routine anti-HIV-1 screening disproportionately were first-time donors and men with exclusively male sexual contacts. The actuarial probability of a person's developing AIDS within 7 years after donation was 40 percent; the probability of a person's dying of AIDS was 28 percent. AIDS developed more often when the donor was p24 antigen-positive at donation. Over a 3-year period, significant decreases occurred in CD4+, CD2+CD26+, CD4+CD29+, and CD20+CD21+ counts, but not in CD8+ subsets, CD20+, or CD14+. CONCLUSION: The high proportions of first-time donations and exclusively homosexual men among seropositive donors suggest that test-seeking may have contributed to the high HIV-1 prevalence in the repository. Implementation of alternative test sites when routine donor screening began in 1985 may have averted many high- risk donations. The disease course in HIV-1-infected donors had the same wide spectrum of immunologic and clinical manifestations as were reported for other cohorts.     

Changes in immunological and virological parameters in HIV-1 infected subjects following leukapheresis

In order to assess immune responses during HIV-1 therapeutic immunization, a large number of blood mononuclear cells (PBMC) are needed. Clinical tolerance and safety, as well as changes in immunological and virological parameters, were assessed, following leukapheresis in HIV-1 infected subjects with CD4(+) cell count >200 x 10(6)/l. PBMC were collected using a Fenwal CS3000 cell separator in 29 subjects with mean CD4(+) cell counts of 503 x 10(6)/l (range 172-1,119) and viral load of 2.5 log(10) copies/ml (range <1.7-5.4). Twenty-four (83%) subjects were on antiretroviral therapy while 5 (17%) were untreated. The blood volume processed was 7 L over a period of 3 hours. A mean value (+/- standard error) of 82 +/- 26 x 10(9)/l lymphocytes was collected by a single apheresis in a mean volume of 200 +/- 1.8 ml, containing 9.0 +/- 1.3 x 10(9)/l CD4(+) and 10.2 +/- 1.3 x 10(9)/l CD8(+) cells. The leukapheresis procedures were well tolerated and no immediate or delayed side effects were observed within 90 days of follow-up. No changes from blood pre-leukapheresis values were detected for white blood cells, lymphocytes, monocytes, CD8(+), CD34(+), naive and memory CD4(+) cell counts immediately after, 1 h, 7 days, or within 90 days after leukapheresis. However, absolute CD4(+) cell counts and percentage significantly increased from pre-leukapheresis values after 1 h (530 +/- 43 vs. 700 +/- 75 cell x 10(6)/l; 32.6 +/- 1.6 vs. 36.9 +/- 1.9%; P < 0.001 for both paired t-tests) before returning to pre-leukapheresis levels on day 7. No significant changes in viral load from pre-leukapheresis levels in treated or untreated subjects were detected at any time points. We conclude that leukapheresis in HIV-1 infected subjects with CD4(+) cell counts >200 x 10(6)/l is safe and induces a transient increase in the absolute and percentage of CD4(+) cell count without enhancing viral replication.     

肝脏间质树突状细胞在多器官功能障碍综合征中的变化与意义

目的探讨肝脏间质树突状细胞在多器官功能障碍综合征（MODS）免疫紊乱机制中的影响与作用。方法150只C57BL／6小鼠经腹腔注射酵母多糖复制MODS模型，随机分为正常对照组和致伤后3～6h、12～48h、5～7d及10～12d组。观察各组小鼠肝脏间质树突状细胞的形态学变化及其表面标记物CD11c、CD205、CD80和I—A^B的表达水平；用流式细胞术检测各组外周血CD4^＋与CD8^＋的T细胞数量及CD4’／CD8’比值。结果急性损伤期（12～48h）肝脏间质树突状细胞大量增生，CD11c、CD205、CD80和I—A^b表达均较正常对照组显著上升（P均〈0．01），外周血T细胞CD4^＋／CD8^＋比值则明显下降（P〈O．01）；功能衰竭期（10～12d）肝脏间质树突状细胞继续增生，但CD205、CD80和I—A^b表达较急性损伤期显著减少（P〈0．05或P〈0．01），外周血T细胞CD4^-／CD8^＋比值下降至最低。结论肝脏间质树突状细胞参与并影响了MODS中肝脏局部与全身免疫失衡及免疫抑制过程。     

Ribavirin disposition in high-risk patients for acquired immunodeficiency syndrome

Ribavirin is a broad-spectrum antiviral drug that has in vitro activity against human immunodeficiency virus. To determine the kinetics of ribavirin, 17 symptom-free homosexual men with lymphadenopathy were studied. Single doses of ribavirin, 600, 1200, or 2400 mg, were given orally or intravenously. The plasma ribavirin concentration-time profiles were well fitted by a three-compartment open model. Ribavirin followed linear kinetics over the dose range studied. The mean 1-hour postinfusion concentrations after intravenous ribavirin, 600, 1200, and 2400 mg, were 8.0, 19.7, and 37.1 mumol/L, respectively. The mean +/- SD plasma beta-phase half-life, terminal-phase (gamma) half-life, and volume of distribution at steady state were 2.0 +/- 1.1 hours, 35.5 +/- 14.0 hours, and 647 +/- 258 L, respectively. The mean ribavirin renal clearance and total body clearance were 99 +/- 30 and 283 +/- 37 ml/min, respectively. After an oral dose of 600, 1200, and 2400 mg, the mean peak plasma ribavirin concentrations (which occurred 1.5 hours after administration) were 5.1, 9.9, and 12.6 mumol/L, respectively. The mean absorption half-life and bioavailability of ribavirin were 0.5 hour and 45%. Ribavirin had no plasma protein binding and the drug accumulated within red blood cells. In conclusion, ribavirin is incompletely absorbed from the gastrointestinal tract, its renal excretion accounts for approximately one third of the drug's elimination, and drug accumulation (greater than threefold) will result with repetitive dosing at the 6- to 8-hour dosing interval currently used.     

Foscarnet-induced changes in plasma concentrations of total and ionized calcium and magnesium in HIV-positive patients

The time course and magnitude of foscarnet-induced changes in plasma concentrations of total and ionized calcium and magnesium were investigated in 13 male HIV-positive patients who had no active cytomegalovirus-associated disease. The patients had a mean age of 36 years (range 25-49 years) and a mean CD4 cell count of 550 cells/mm3 (range 130-1280 cells/mm3). Peak (mean +/- SD) plasma concentrations of foscarnet (0.89+/-0.10 mmol/l) were seen at the end of the period of drug infusion (90 mg/kg of foscarnet was infused over 2 hours) and declined with a terminal half-life of 5.7+/-0.7 hours. Plasma concentrations of total calcium declined over an 8-hour period, with the lowest concentration occurring after 4 hours (baseline: 2.29+/-0.09 mmol/l; lowest: 2.18+/-0.07 mmol/l; P < 0.001). By contrast, the lowest plasma concentration of ionized calcium occurred after 2 hours (baseline: 1.25+/-0.04 mmol/l; lowest: 0.99+/-0.05 mmol/l; P < 0.001), before gradually recovering to baseline levels over the next 10 hours. The mean maximal decrease in total calcium was 0.11+/-0.06 mmol/l, compared with 0.26+/-0.04 mmol/l for ionized calcium (P < 0.001). Plasma concentrations of total magnesium declined from 0.79+/-0.06 mmol/l (baseline) to 0.74+/-0.04 mmol/l (P < 0.05) after 4 hours and remained at this level after 8 hours. However, plasma concentrations of ionized magnesium fell steeply from 0.56+/-0.03 mmol/l to 0.39+/-0.03 mmol/l at 2 hours (P < 0.001), followed by a gradual recovery over the next 10 hours. The mean maximal decrease in total magnesium was 0.05+/-0.08 mmol/l, compared with 0.18+/-0.03 mmol/l (P < 0.001) for ionized magnesium. In summary, we found that foscarnet-induced changes in the plasma concentrations of total calcium and magnesium were dissociated from the corresponding changes in ionized calcium and magnesium. The maximal decreases in the plasma concentrations of total calcium and magnesium were smaller in magnitude and occurred much later than did the changes in ionized calcium and magnesium. The relative changes in the plasma concentration of ionized magnesium were greater than those of ionized calcium, indicating that foscarnet binds preferentially to the magnesium ion.     

The neonatal immune response to washed and irradiated red cells: lack of evidence of lymphocyte activation

A total of 21 neonatal infants (11 males and 10 females) were evaluated for lymphocyte subpopulation changes and cellular activation following the receipt of washed and gamma-irradiated red cells. The mean donor exposure was 2 +/- 1.5 donors, and the mean white cell concentration of each 10-mL-per-kg transfusion was 2 x 10(7) cells. A total of 2800 rad (28 Gy) was delivered to each red cell unit prior to washing. The lymphocyte subsets CD3+, CD4+, CD8+, CD19+, CD3+/CD25+, CD3+/HLA-DR, CD4+/CD45RA, CD4+/CDw29, and CD4+/ICHL-1 were analyzed, as were plasma gamma-interferon and neopterin levels, before and after blood transfusion. Posttransfusion samples were obtained from 3 to 12 days after the last blood transfusion. There were no posttransfusion changes in the percentage of lymphocyte subsets analyzed. Furthermore, overlay-histogram analysis of pretransfusion and posttransfusion CD45RA-, CDw29-, and UCHL-1-positive helper T cells failed to reveal a shift in mean channel fluorescence intensity, which is indicative of a lack of cellular activation. Gamma-interferon levels remained unchanged after transfusion (range, 90 +/- 5.9 to 95.5 +/- 5.3 pg/mL), as did neopterin levels (range, 3.7 +/- 1.5 to 4.6 +/- 1.5 ng/mL). This study could not find any evidence, by either cellular or humoral markers, of the activation of neonatal lymphocytes by transfusion. It is hypothesized that this failure to observe lymphocyte activation is due to the low number of donor white cells present in washed, irradiated red cells and/or to a lack of recipient recognition of transfused, allogeneic, donor white cells.     

Antibodies to human T-cell lymphotropic virus type III in promiscuous healthy homosexual men. Relation to immunological and clinical findings

Antibodies to human T-cell lymphotropic virus type III (HTLV-III Ab) were present in twenty-one out of sixty-four asymptomatic promiscuous homosexual men from Copenhagen. The presence of HTLV-III Ab was associated with lymphadenopathy (P less than 0.0005), cytomegalovirus isolation (P less than 0.01), low skin test reactivity (P less than 0.01) and episodes of fever within the 2 month period prior to investigation (P less than 0.05). No significant differences occurred in the total number of T-cells, T-suppressor cytotoxic cells, T-helper cells or helper to suppressor ratio (H/S ratio) between HTLV-III Ab positive and negative homosexuals. An H/S ratio less than or equal to 1.0 was significantly more frequent in homosexual men who both had HTLV-III Ab and excreted cytomegalovirus (P less than 0.01). The H/S ratio of HTLV-III negative homosexuals were significantly lower than that of the controls suggesting that a non-HTLV-III related immunosuppression occurs among homosexuals. Within 2 years after the investigation AIDS or the AIDS related complex developed in three of the men, who at the first investigation all had HTLV-III Ab, alterations in T-lymphocyte subsets and cutaneous anergy. It is suggested that a combination of T-cell subset determination and determination of HTLV-III Ab may provide more valuable prognostic information than isolated determination of HTLV-III Ab.     

Infant feeding effects on flow cytometric analysis of blood

Flow cytometric analysis was performed on purified mononuclear cells isolated from whole blood samples of 11 adults, 7 breast-fed (BF) infants and 11 formula-fed (FF) infants, mean ages 34.2 +/- 4.3 years, 6.3 +/- 1.3 months, and 6.2 +/- 1.2 months, respectively. Infants were receiving at least 70% of calories from formula or breast milk. Infant mononuclear cell populations contained a higher percentage of lymphocytes and a lower percentage of monocytes compared with adults. Within the lymphocyte population, infants had a higher CD4+/CD8+ ratio (T helper-inducer/T cytotoxic-suppressor), a higher percentage of CD19+ (pan B) and CD4+ cells, and a lower percentage of CD8+ and CD16+ (natural-killer) cells compared with adults. CD3+ (pan T) and CD4+ lymphocyte percentages were higher and CD19+ lymphocyte percentages were lower in FF compared with BF infants. Although sample size is small, our data indicate that diet may influence lymphocyte subset distribution during infancy when the majority of calories is derived from infant formula or human milk.     

Autoantibodies to TNFalpha in HIV-1 infection: prospects for anti-cytokine vaccine therapy.

Tumor necrosis factor alpha (TNFalpha) is a proinflammatory cytokine principally involved in the activation of lymphocytes in response to viral infection. TNFalpha also stimulates the production of other cytokines, activates NK cells and potentiates cell death and/or lysis in certain models of viral infection. Although TNFalpha might be expected to be a protective component of an antiviral immune response, several lines of evidence suggest that TNFalpha and other virally-induced cytokines actually may contribute to the pathogenesis of HIV infection. Based on the activation of HIV replication in response to TNFalpha, HIV appears to have evolved to take advantage of host cytokine activation pathways. Antibodies to TNFalpha are present in the serum of normal individuals as well as in certain autoimmune disorders, and may modulate disease progression in the setting of HIV infection. We examined TNFalpha-specific antibodies in HIV-infected non-progressors and healthy seronegatives; anti-TNFalpha antibody levels are significantly higher in GRIV seropositive slow/non-progressors (N = 120, mean = 0.24), compared to seronegative controls (N= 12, mean = 0.11). TNFalpha antibodies correlated positively with viral load, (P = 0.013, r = 0.282), and CD8+ cell count (P = 0.03, r = 0.258), and inversely with CD4+ cell count (P = 0.003, r = - 0.246), percent CD4+ cells (P = 0.008, r = -0.306), and CD4 :CD8 ratio (P = 0.033, r = - 0.251). TNFalpha antibodies also correlated positively with antibodies to peptides corresponding to the CD4 binding site of gp160 (P = 0.001, r = 0.384), the CD4 identity region (P = 0.016, r = 0.29), the V3 loop (P = 0.005, r = 0.34), and the amino terminus of Tat (P = 0.001, r = 0.395); TNFalpha antibodies also correlated positively with antibodies to Nef protein (P = 0.008, r = 0.302). The production of anti-TNFalpha antibodies appears to be an adaptive response to HIV infection and suggests the potential utility of modified cytokine vaccines in the treatment of HIV infections as well as AIDS-related and unrelated autoimmune and CNS disorders.     

非霍奇金淋巴瘤患者外周血CD4+CD25high调节性T细胞研究

本研究分析B细胞非霍奇金淋巴瘤(B-NHL)患者外周血T细胞亚群及CD4+CD25high调节T(Tr)细胞比例及其变化规律,初步探讨B-NHL免疫抑制机制,以及化疗对此免疫抑制功能的影响.采用流式细胞术检测42例初治B-NHL患者、36例化疗后达CR/PR患者及15例正常健康者(对照组)外周血CD3+、CD4+、CD8+和CD4+CD25highT细胞的比例.结果显示B-NHL患者CD3+及CD4+T细胞比例、CD4/CD8比值均低于正常对照组,它们依次为(68.33±15.27)%,对照(72.06±9.26)%;(34.47±12.84)%,对照(42.45±9.2)%;1.36±0.26,对照1.92±0.20,但CD4+CD25high Tr细胞比例明显高于正常对照组,为(4.10±1.21)%,对照(2.04±1.03)%,(P＜0.001).化疗后组CD4/CD8比值低于化疗前组(P＜0.05);而外周血CD4+CD25high Tr细胞比例,显著高于化疗前组和对照组(P＜0.01).结论B-NHL初治化疗前及化疗后患者外周血CD4+CD25high Tr细胞比例都显著升高,提示CD4+CD25high Tr细胞可能是B-NHL患者免疫抑制的重要原因之一.     

Analysis of IGG and IGG4 in HIV-1 seropositive patients and correlation with biological and genetic markers.

We have compared the levels of immunoglobulins G (IgG) and G4 (IgG4) in extreme seropositive patients from the GRIV cohort consisting of 168 patients with slow progression (SP) and 60 with rapid progression (RP) as well as in 173 healthy controls. IgG levels were significantly higher in SP patients than in RP patients (P = 0.008), both higher than in seronegative individuals. IgG4 levels were significantly lower in SP patients than in RP patients (P = 0.001), both lower than in seronegative individuals. We tried to correlate these levels with biological parameters (CD4(+) and CD8(+) cells, total lymphocytes, white blood cell counts, percentage of CD4(+) cells, and viral load) as well as with genetic markers from Th1/Th2 cytokines (IL2, IL4, IL6, IL10, IL13, and IFNgamma). IgG levels were correlated with the percentage of CD4(+) cells in SP while IgG4 levels were correlated with CD8(+) cell count in SP and with percentage of CD4(+) cells in RP patients. Among the parameters measured in SP patients at the time of inclusion in the study, the best predictor of progression towards AIDS was the viral load, the best predictor for stability was CD4(+) cell count, but overall, the best predictor for SP evolution (stability vs. progression) appeared to be the percentage of CD4(+) cells. Interestingly, correlations between the levels of IgG or IgG4 and the cytokine gene polymorphisms were found, notably in the IL10 gene.