Varicella zoster virus meningitis complicating sodium stibogluconate treatment for cutaneous leishmaniasis

Sodium stibogluconate (Pentostam(R); GlaxoSmithKline) is a pentavalent antimonial compound used in the treatment of leishmaniasis, which has an association with reactivation of varicella zoster virus (VZV). We report the first known case of an immunocompetent adult who developed VZV aseptic meningitis and dermatomal herpes zoster during treatment with sodium stibogluconate.     

Subclinical varicella-zoster virus viremia, herpes zoster, and T lymphocyte immunity to varicella-zoster viral antigens after bone marrow transplantation.

Bone marrow transplant (BMT) recipients were evaluated for subclinical varicella-zoster virus (VZV) viremia and symptoms of herpes zoster after transplantation. Viremia was demonstrated by testing peripheral blood mononuclear cells using polymerase chain reaction and was documented in 19% of 37 patients. When reactivation was defined as herpes zoster and/or subclinical VZV viremia, 41% of VZV-seropositive BMT recipients experienced VZV reactivation. None of 12 patients tested before VZV reactivation had T lymphocyte proliferation to VZV antigen (mean stimulation index, 1.0 +/- 0.42 [SD] at less than 100 days; 12.0 +/- 6.03 at greater than 100 days [P = .003]). Among patients tested at greater than 100 days, 5 (63%) of 8 with detectable T cell proliferation had subclinical or clinical VZV reactivation compared with none of 6 who lacked VZV T cell responses. Recovery of VZV-specific cytotoxic T lymphocyte function was observed in 50% of BMT patients, but BMT recipients had significantly fewer circulating cytotoxic T lymphocytes that recognized VZV immediate early protein (P = .03) or glycoprotein I (P = .004) than did healthy VZV immune subjects. In vivo reexposure to VZV antigens due to subclinical VZV viremia or symptomatic VZV reactivation may explain the recovery of virus-specific T cell immunity after BMT.     

Effects of cyclosporin A upon humoral and cellular immune parameters in insulin-dependent diabetes mellitus type I: a long-term follow-up study

Patients who had been included in a randomized double-blind placebo-controlled trial on the efficacy of cyclosporin A (CyA) in producing remissions in insulin-dependent diabetes mellitus (IDDM) type I were investigated for humoral and cellular immunologic parameters. Whereas metabolic derangement before the initiation of insulin treatment led to small but significant decreases in the percentage of CD4-positive lymphocytes as well as of the activity of natural killer (NK) cells and antibody-dependent cellular cytotoxicity (ADCC), the administration of CyA did not influence any of the immunologic parameters tested, which included proliferative lymphocyte responses to mitogens and alloantigens and serum concentrations of immunoglobulins G, A and M. Thus NK cell activity, ADCC as well as the percentage of CD4-positive lymphocytes returned to normal levels in parallel with the normalization of glycosylated haemoglobin (HbAlc), but were not further influenced in their course by the administration of CyA, as compared with patients receiving placebo. Interferon-induced augmentation of NK cell activity did not differ between patients with IDDM on placebo and those under CyA therapy. All other investigated parameters also remained unchanged during the time of CyA therapy. We conclude that metabolic derangement leads to a reversible disturbance of certain cellular immune functions, but their normalization achieved by insulin treatment and their further course remains uninfluenced by the administration of CyA.     

Immune status in Crohn's disease. VI. Immunoregulation evaluated by multiple, distinct T-suppressor cell assays of lymphocyte proliferation, and by enumeration of immunoregulatory T-lymphocyte subsets

In 28 patients with Crohn's disease, 6 patients with ulcerative colitis, and 34 healthy controls, immunoregulatory function of peripheral blood mononuclear cells was investigated by evaluating the suppression of lymphocyte proliferative responses to mitogens (phytohemagglutinin, concanavalin A, pokeweed mitogen) and to allogeneic lymphocytes (mixed lymphocyte culture) using simultaneously five functional assays as follows: (a) spontaneous T-suppressor-cell activity, (b) concanavalin A-generated T-suppressor-cell activity, both with (3000 rads) and without irradiation of suppressor cells, and (c) allogeneic mixed lymphocyte culture-generated T-suppressor-cell activity, again both with and without irradiation. Concanavalin A- and mixed lymphocyte culture-generated T-suppressor-cell activities were evaluated both in the autologous and the allogeneic system. In addition, using monoclonal antibodies, we determined proportions of T-helper and T-suppressor/cytotoxic lymphocytes. Inactive patients did not differ from normal either in the proportions of immunoregulatory lymphocytes or in the suppression of the various lymphocyte proliferative responses in any of the five T-suppressor-cell assays evaluated. In patients with active disease, however, an impairment of suppression of phytohemagglutinin-, pokeweed mitogen-, and mixed lymphocyte culture-stimulated proliferation of autologous lymphocytes was observed in the concanavalin A-generated, irradiated suppressor assay. In the spontaneous suppressor assay, suppression of phytohemagglutinin- and concanavalin A-stimulated lymphocyte proliferation was significantly lower in active disease than in remission. Thus, in peripheral blood of patients with Crohn's disease who are in remission, there is no indication for an immunoregulatory defect in any of the evaluated assay systems. Single selective, moderate defects in suppression of proliferation of various lymphocyte subpopulations are restricted to active disease.     

Proportional and functional studies of the infiltrating lymphocytes in the parotid gland of Sj?gren's syndrome associated with rheumatoid arthritis

Lymphocyte subpopulations and functions were examined in the salivary (parotid) gland lymphocytes (SGL) obtained as a cell suspension from a patient with Sj?gren's syndrome associated with rheumatoid arthritis, in comparison with peripheral blood lymphocytes (PBL). Serial studies on the lymphocyte subsets in PBL using monoclonal antibodies to helper or suppressor T cell subsets (OKT4 or OKT8) demonstrated a decreased proportion of the OKT8 subset (OKT4/OKT8 ratio: 7.1-34.0). Major infiltrating cells in the gland were surface immunoglobulin-bearing B cells, and 23-35% of the SGL were T cells by both the E-rosetting method and OKT3-monoclonal antibody reactivity. Moreover, OKT4/OKT8 ratios were definitely lower in the SGL (1.0 and 1.7) than those in the PBL of the patient. Mitogen-induced lymphocyte proliferative responses of the SGL were markedly diminished, although the possible participation of defective macrophages was considered. The autologous mixed lymphocyte reaction was low in both PBL and SGL. PBL of the patient showed normal proliferative responses to mitogens except for PWM stimulation. Suppressor effects of the SGL for the proliferative responses of autologous and allogeneic PBL were demonstrated. Con A-induced suppressor function was inducible in the SGL, whereas that function could not be demonstrated in the patient's PBL.     

Varicella vaccination in HIV-1-infected children after immune reconstitution

BACKGROUND: HIV-1-infected children have an increased risk of severe chickenpox. However, vaccination is not recommended in severely immunocompromised children. OBJECTIVE: Can the live-attenuated varicella zoster virus (VZV) Oka strain be safely and effectively given to HIV-1-infected children despite previously low CD4 T-cell counts? METHODS: VZV vaccine was administered twice to 15 VZV-seronegative HIV-1-infected children when total lymphocyte counts were greater than 700 lymphocytes/microl, and six HIV-negative VZV-seronegative siblings. Weekly clinical follow-up and sampling were performed. RESULTS: None of the children developed any clinical symptom or serious adverse reaction after immunization. Only nine (60%) of the HIV-1-infected children had VZV-specific antibodies after two immunizations, whereas 100% of the siblings seroconverted. Age at baseline was negatively correlated with the VZV IgG titre at 6 weeks after the second vaccination in HIV-1-infected children. VZV-specific antibody titres after two immunizations were at a similar level to those found after wild-type infection in non-vaccinated HIV-1-infected patients, but significantly lower than in HIV-negative siblings. Importantly, VZV-specific T-cell responses increased after vaccination and were comparable in both groups over time. Documented wild-type VZV contact in three vaccinated patients did not result in breakthrough infections. CONCLUSION: VZV vaccination of previously immunocompromised HIV-1-infected children was safe. Vaccination induced specific immune responses in some of the vaccinated HIV-1-infected children, suggesting that previously immunocompromised individuals are protected against severe forms of varicella.     

Deoxycoformycin-induced immunosuppression in patients with hairy cell leukemia

Immune function in patients with hairy cell leukemia (HCL) was examined serially during treatment with alternating monthly cycles of recombinant interferon alpha-2a and 2'-deoxycoformycin (dCF). At presentation, most patients had normal numbers of T lymphocytes and their cells had normal proliferative responses to mitogens [phytohemagglutinin (PHA) and concanavalin A (Con A)] and alloantigens. Patients had severe monocytopenia, decreased delayed-type hypersensitivity (DTH) reactions, and decreased peripheral blood natural killer (NK) activity. Treatment caused a profound decrease in all lymphocyte subpopulations. T cells were more affected than B cells or NK cells. Numbers of CD4+ and CD8+ lymphocytes decreased to levels less than 200 cells/microliters in all patients during treatment. This decrease in T cell number was associated with a marked decrease in proliferative responsiveness to PHA, Con A, and alloantigens. These abnormalities persisted throughout the 14 months of treatment and have continued for up to 6 months beyond discontinuation of treatment. NK cell activity increased during treatment, but cycled depending on the phase of treatment; highest activities were observed after interferon (IFN)-alpha and lower levels of activity were observed after dCF. DTH responses generally did not improve during therapy. Levels of IgM, IgG, IgA, and IgD did not change during treatment, but IgE levels rose in most patients. All immunosuppressive effects were attributable to dCF since patients receiving IFN-alpha 2a alone did not exhibit these same immunosuppressive effects, and patients receiving dCF alone after IFN failure exhibited similar abnormalities. Despite this severe immunosuppression from dCF, life-threatening opportunistic infections have not been observed in our patient population. Six patients developed localized Herpes zoster infection among 21 patients who had received dCF. Pending the results of long-term follow-up, we recommend that dCF be reserved for patients who have failed splenectomy and IFN therapy.     

Selective impairment of lymphocyte reactivity to varicella-zoster virus antigen among untreated patients with lymphoma.

Herpes zoster is a frequent complication of lymphoreticular malignancy. In this study two assays of in vitro cellular immune response to varicella-zoster virus (VZV) antigen, lymphocyte transformation and interferon production, were performed in normal subjects with recent and remote VZV infection. The responses of patients with lymphoma were measured before treatment and during long-term remission and then compared with those of normal subjects. Despite levels of antibody to VZV that were equivalent to those in normal subjects, 44% of the untreated lymphoma patients showed a lower transformation response to VZV antigen than the normal patients. Production of interferon in response to VZV antigen was absent in 32% of the untreated patients. In contrast, lymphocyte responses in untreated patients to herpes simplex virus antigen were within the range observed in a normal population. Interferon production by lymphocytes in response to cytomegalovirus antigen was also lower among untreated lymphoma patients than among normal patients, but lymphocyte transformation was not. Twenty-two percent of lymphoma patients in long-term remission continued to have diminished cellular immune responses to VZV antigen. Observations in these patient populations and in normal subjects with acute herpes zoster suggest that deficiencies in in vitro lymphocyte responses may correlate with increased susceptibility to clinical infection with VZV.     

Abnormalities of CD4+ T lymphocyte proliferative responses from patients with recently diagnosed insulin-dependent diabetes mellitus

To investigate the abnormalities of cell-mediated immunity in patients with recently diagnosed insulin-dependent diabetes mellitus (IDDM), we studied the responses of the two major T lymphocyte subsets from peripheral blood lymphocytes (PBL) to mitogen stimulation. Samples for PBL were obtained from a group of IDDM patients and from a group of normal controls. CD4+ and CD8+ T cells were isolated and were subsequently stimulated with three specific lymphocyte mitogens, namely Phytohemagglutinin (PHA), Concanavalin A (Con A) and Pokeweek mitogen (PWM). The proliferative response was measured by incorporation of radioactive thymidine in lymphocyte cultures which were stimulated by the three mitogens. The responses of CD8+ T cells from IDDM patients and from controls were not significantly different. However, CD4+ T cells from IDDM patients showed significantly depressed responses to PHA and Con A and to a much lesser extent to PWM. These data provide new information regarding the CD4+ T lymphocyte abnormalities found in patients with IDDM.     

T-cell subset alterations and lymphocyte responsiveness to mitogens and antigen during severe primary infection with HIV: a case series of seven consecutive HIV seroconverters

Seven consecutive patients who presented with a severe acute mononucleosis-like illness associated with HIV seroconversion were evaluated by T-cell subset enumerations and measurements of lymphocyte transformation responses to mitogens and antigen during both their primary illness and a 1-year follow-up period. We observed a characteristic pattern of response to primary HIV infection; initial lymphopenia was followed by CD8 lymphocytosis and inversion of the CD4:CD8 ratio. During follow-up, the CD8 count gradually returned to normal, whereas the CD4:CD8 ratio remained inverted because of a relatively low number of CD4 lymphocytes. Primary infection was followed by prolonged and severe cellular hyporesponsiveness to both mitogens and antigen. At the last follow-up, responses to pokeweed mitogen were still severely impaired, with a median 19% (range 7-50%) of that observed in healthy controls. We conclude that severe primary HIV infection may be followed by sustained lymphocyte hyporesponsiveness, a sustained low percentage of CD4 lymphocytes and sustained inversion of the CD4:CD8 ratio.     

Cellular and humoral immunity to varicella zoster virus glycoproteins in immune and susceptible human subjects

To further delineate the immune responses that protect against serious primary varicella zoster virus (VZV) infection and inhibit viral reactivation, antibody responses and T lymphocyte reactivity to three major VZV glycoproteins, gpI, gpII, and gpIII, were studied. Individual viral glycoproteins were purified using murine monoclonal antibodies. Cellular immunity was measured by lymphocyte proliferation. Antibody responses were tested in enzyme-linked immunosorbent assays. Individual glycoproteins induced VZV-specific proliferation by mononuclear cells from 15 of 20 immune subjects. Serologic responses to the VZV glycoproteins occurred in 16 of 20 immune subjects. Of note, gpII served as a potent T and B cell antigen during both acute infection and convalescence. Cell-mediated responses to the glycoprotein antigens represented proliferation by T lymphocytes and required antigen presentation by adherent mononuclear cells. These findings indicate that virally encoded glycoproteins contain epitopes that stimulate VZV-specific cellular and humoral immune responses.     

The clinical outcome of autoimmune thrombocytopenic purpura patients is related to their T cell immunodeficiency

Summary. In this work we have furthered the understanding of the alterations of T lymphocytes from 29 patients with active autoimmune thrombocytopenic purpura (ATP) and the clinical significance of their lymphocytes. An increased percentage of in vivo activated (CD25+ and DR+) T lymphocytes was found in ATP patients with respect to that found in 22 healthy controls. The function of these T cells measured as the proliferative response to polyclonal mitogenic signals is heterogeneously impaired in ATP patients. T lymphocytes from 65·5% (19/29) of the ATP patients showed a decreased proliferative response to these mitogenic signals. This functional alteration is associated with a redistribution of the T cell compartment in these patients' peripheral blood since a significant decrease of CD4+ T lymphocytes was found.
We have also found that the impairment of the T cell function is different in the diverse clinical situations of the disease. Those with stable, untreated disease showed a marked decrease in the T cell proliferative response to mitogens. Furthermore, those patients who did not respond either to steroids or to splenectomy showed significantly reduced T lymphocyte blastogenesis after phytohaemagglutinin (PHA) stimulation in comparison to that found in responding patients.     

Peripheral blood T and B cell characteristics in a patient with severe combined immune deficiency (SCID) maintained in a gnotobiotic environment.

Peripheral blood lymphocytes obtained at 24-30 months after birth from a male with X-linked severe combined immune deficiency maintained in a gnotobiotic environment were characterized by T and B cell surface markers. A high proportion (55-80 percent) of circulating lymphocytes bore surface IgM as detected by direct immunofluorescence. A receptor for the activated C3 complement component was detected on 27-47 percent of his lymphocytes. Only 4-12 percent of the peripheral blood lymphocytes formed spontaneous rosettes with sheep erythrocytes (E-R). In general, no blastogenesis was detected in lymphocyte cultures stimulated with pokeweed mitogen or phytohemagglutinin although transient slightly positive responses to both mitogens were occasionally observed. Incubation of lymphocytes with bovine thymosin Fraction V did not increase the percentage of E-R nor induce lymphocyte blastogenesis in the presence of phytohemagglutinin.     

Immune function and anti-HTLV-I/II status in anti-HIV-1-negative intravenous drug users receiving methadone.

PURPOSE: The study objective was to evaluate the effects of long-term methadone use and human T-cell leukemia virus (HTLV) types I and II seropositivity on the distribution of lymphocyte subsets and on lymphocyte function as measured in vitro in intravenous drug users seronegative for human immunodeficiency virus type 1 (HIV-1). PATIENTS AND METHODS: Anti-HIV-1-negative intravenous drug users receiving methadone maintenance therapy (n = 24) were studied in a Veterans Administration drug abuse treatment center. These subjects were compared to 38 age- and sex-matched control subjects who did not abuse drugs. HIV-1 and HTLV serostatus was determined by repetitive enzyme-linked immunosorbent assay and confirmed by immunoblot. Lymphocyte subsets were determined by two-color flow cytometry. Lymphocyte function was measured by proliferative response to plant mitogens and by natural killer (NK) cell-mediated cytotoxicity to a tumor cell target. RESULTS: Significant differences were seen in lymphocyte phenotype in the methadone-treated group, with elevations in the T-cell helper subset CD4+CD26+; in CD8 and CD8+I2+ cells, suppressor/cytotoxic T lymphocytes, and activated suppressor/cytotoxic T cells; and in CD2+CD26+ cells and activated total T lymphocytes. Lymphocyte function was suppressed in the methadone group, with poor responses to pokeweed mitogen and phytohemagglutinin in culture. Moreover, NK-cell cytotoxicity was significantly reduced in the methadone group. None of these immunologic differences were attributable to HTLV serostatus. CONCLUSION: The immune abnormalities seen suggest that a clinically significant degree of immune impairment exists in methadone-treated intravenous drug users. However, these abnormalities could not be explained by the presence of other retroviruses in this HIV-1-negative study group, as there was no significant difference in immune function when HTLV-seropositive patients were compared to HTLV-seronegative subjects treated with methadone.     

Cell-mediated immunity in rheumatic diseases

Lymphocyte responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen were tested in normal patients and in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), scleroderma (PSS), other connective tissue disease, and other illnesses. The relationship of lymphocyte response to diagnosis, therapy, and T- and B-lymphocyte populations was analyzed. Additional studies included the determination of proliferative responses of various combinations of purified T and B lymphocytes cultured with plant mitogens. Lymphocytes from patients with RA and SLE incorporated significantly less thymidine in the presence of plant mitogens as compared to normal and comparably ill subjects. Treatment had no effect on mitogen response. Responses to all three mitogens correlated closely in patients with RA, SLE, or PSS; no correlation was noted between the response to mitogen of lymphocytes in culture and the number of T cell ultured.     

Varicella-zoster virus (VZV)-specific cytotoxicity after immunization of nonimmune adults with Oka strain attenuated VZV vaccine.

Cytotoxic, proliferative, and serum IgG antibody responses to varicella-zoster virus (VZV) were measured monthly in 29 young adults for 3 months following primary immunization with the Oka strain attenuated VZV vaccine. No subjects had lymphocytes stimulated to VZV-specific cytotoxicity at study entry although lymphocytes from 2 subjects proliferated when stimulated by VZV antigen. The percentages of subjects with positive major histocompatibility complex class II-restricted cytotoxic responses at 1, 2, and 3 months after immunization were 54%, 69%, and 66%, respectively. Correlations between cytotoxic, proliferative, and antibody responses were highest in the first month after immunization; lower but still statistically significant after the second month; and not apparent by the third month. The data suggest that antibody and cell-mediated immune responses to VZV immunization develop in parallel after immunization, but these effector mechanisms are independently regulated by 3 months after immunization.     

Proliferative response of mononuclear cells from HIV-infected patients to B-cell mitogens: effects of lymphocyte subset frequency, T-cell defects and prostaglandins.

Proliferative responses of mononuclear cells from patients seropositive for human immunodeficiency virus to B-cell mitogens are severely depressed compared with those of controls. The role of several immunoregulatory phenomena was analyzed. Experimental results show that addition of exogenous lymphokines to cultures increases responses to anti-mu and SAC. Addition of indomethacin to cultures greatly increases the SAC response and causes a smaller increase in the pokeweed mitogen (PWM) response. When both exogenous lymphokines and indomethacin are present in cultures, responses of patients' cells to all three mitogens are positively correlated with the percentage of CD4+ T cells and negatively correlated with the percentage of CD8+ T cells. Responses to anti-mu and SAC are also positively correlated with the percentage of B cells in these cultures. On the basis of these correlations between B-cell responses and lymphocyte subset frequency, patients' B-cell responses can be mathematically corrected to estimate the responsiveness of the B cells in the presence of normal numbers of CD4+ and CD8+ cells. These corrected responses for all three mitogens are virtually identical to control responses. Furthermore, responses of enriched B-cell populations from HIV+ subjects and normal controls to SAC were not significantly different when assays were performed in the presence of indomethacin and exogenous lymphokines. These results suggest that B cells from HIV+ patients are inherently normal in their responsiveness to B-cell mitogens. The depressed function is imposed upon them as a result of the abnormal frequency of lymphocyte subsets in the blood, by increased prostaglandin production, and deficient lymphokine production.     

Impact of the duration of antiviral prophylaxis on rates of varicella-zoster virus reactivation disease in autologous hematopoietic cell transplantation recipients

Varicella-zoster virus (VZV) reactivation is a relatively common cause of morbidity following autologous hematopoietic cell transplant (auto-HCT). The Centers for Disease Control in 2009 recommended extending VZV prophylaxis for 1 year post-transplantation. We retrospectively analyzed rates of VZV reactivation following auto-HCT at our transplant center prior to and after the implementation of extended antiviral prophylaxis in June 2008. The study population was divided into three different cohorts according to the length of VZV prophylaxis as following: (1) prophylaxis until neutrophil recovery to ≥500/μL (n?=?77), (2) prophylaxis for 6 months (n?=?12), or (3) 12 months (n?=?40) post-auto-HCT. All patients received acyclovir 400 mg oral or intravenously twice daily or valacyclovir 500 mg oral daily. For patients in whom VZV reactivation occurred, data was collected on severity of infection, time of onset, treatment, and any associated complications. One hundred twenty-nine patients undergoing auto-HCT between January 1, 2004 and January 31, 2010 were included in the study. There was a significant difference in the rates of VZV reactivation between the neutrophil recovery and 12 months prophylaxis cohorts at 14 % (n?=?11) and 2 % (n?=?1) (P?=?0.04), respectively. VZV reactivation rate in the 6-month prophylaxis group was 17 % (n?=?2), but did not reach statistical significance due to small numbers. In the subset of auto-HCT patients treated with bortezomib, 13 % (n?=?2) developed VZV reactivation in the neutrophil recovery group, while no events occurred in the other two cohorts. Complications of VZV reactivation include post-herpetic neuralgia (n?=?5), severe pain (n?=?3), scarring (n?=?1), and motor weakness (n?=?1); two patients required hospitalization and three patients developed disseminated zoster. Our limited retrospective analysis suggests a significant reduction in rates of post-auto-HCT rates of VZV reactivation with extended 12 months antiviral prophylaxis. VZV reactivation is a significant complication post-auto-HCT, and extended prophylaxis appears to be safe and effective in this setting.     

Lymphocyte subset reconstitution following human allogeneic bone marrow transplantation: differences between engrafted patients and graft failure patients.

To define the relationship between hematopoietic reconstitution and lymphocyte subset analysis in human allogeneic bone marrow transplantation (BMT), we compared lymphocyte subset reconstitution during the first 4 weeks after BMT in nine engrafted patients with that in three graft failure patients using flow cytometry. Marked differences were observed between the two groups. In graft failure patients, the percentage of CD3+ lymphocytes had increased 2 weeks after BMT by over 90% (p less than 0.05). The percentage of CD16+ lymphocytes and CD16+ CD57- lymphocytes did not increase (CD16+ at 3 and 4 weeks: p less than 0.05, CD16+ CD57- at 3 weeks; p less than 0.05, at 4 weeks: p less than 0.01), nor did the percentage of CD8+ 11b+ lymphocytes. The percentage of CD8+ 11b- lymphocytes had increased markedly 2 weeks after BMT (at 2 weeks: p less than 0.05, at 3 and 4 weeks: p less than 0.01). Of particular interest is the difference in the percentage of CD3+, CD16+, and CD8+ CD11b- T cells between the two groups. These cells may play a role in allogeneic bone marrow cell engraftment.     

Cellular immune response analysis of patients with leptospirosis

Peripheral blood mononuclear cells (PBMC) from acute leptospirosis patients with and without acute renal failure were studied in order to investigate the status of cellular immunity in this disease. We analyzed the lymphocyte subsets of leptospirosis patients by immunofluorescence and their responsiveness to the mitogens phytohemagglutinin (PHA) and pokeweed mitogen (PWM). Additionally, we investigated the effect of the patients' sera on normal PBMC proliferative response. We observed a decrease in the CD3+ and CD4+ cell subsets in patients with and without acute renal failure, or in percentage values alone in those who had recovered from renal failure. An increase in the number of B lymphocytes was observed in all patients, compared with controls. This increase in B lymphocytes was seen even in patients who had recovered from renal failure, when the number of CD3+ and CD4+ lymphocytes had already returned to normal levels. The low PHA response observed only with lymphocytes from patients with acute renal failure suggests a suppressive effect. The proliferative response to PWM was comparable to controls, even in the patients with acute renal failure. This latter result and the expansion of the B cell number could be related to leptospiral-derived factor(s). We also showed that sera from patients with and without acute renal failure exerted some inhibitory activity on normal PBMC responses to PHA and PWM. Although the redistribution of lymphocyte subsets and the serum suppressor activity were related to acute renal failure and leptospiral factor(s), we suggest that the cellular immune system was not irreversibly affected, which is compatible with the good prognosis seen in the patients studied.