医源性HIV感染者CD8+细胞非细胞毒性HIV抑制作用的研究

目的 观察医源性HIV感染者CD8+细胞非细胞毒性HIV抑制反应(CNAR),并比较CNAR与CD4细胞计数的关系.方法 免疫磁珠法分离HIV感染者的CD8+细胞,按2:1,1:1,0.5:1和0.25:1的比例,与体外急性感染的CD4+细胞混合培养,测定培养物上清中逆转录酶活性,与阴性对照比较计算病毒抑制率.结果 CNAR活性达到80%病毒抑制率时,CD4<300个/μl组的平均CD8与CD4比例为2.4:1,CD4>300个/μl组的平均CD8与CD4比例为1.3:1,两组间比较差异有统计学意义(P<0.05).结论 HIV感染者的CNAR活性与其CIM细胞计数相关,CD4>300的个体较CD4<300的个体有着更显著的抑制HIV复制的能力.     

CD8+ Cell Anti-HIV Activity Rapidly Increases Upon Discontinuation of Early Antiretroviral Therapy

Introduction  CD8+ lymphocytes can suppress HIV replication without killing the infected cells. This CD8+ cell noncytotoxic anti-HIV response (CNAR) is associated with a beneficial clinical course. Materials and Methods  In this longitudinal study of 16 participants in the Options Project at UCSF, we measured the ability of CD8+ lymphocytes to suppress HIV replication in CD4+ cells during primary HIV infection, early antiretroviral therapy, and after treatment. Results and Discussion  CD8+ lymphocytes from subjects with untreated primary HIV-1 infection strongly suppressed HIV replication. Initiation of antiretroviral therapy during primary HIV-1 infection caused a marked decline in this CNAR. CD8+ cells from these subjects regained anti-HIV activity when early therapy was discontinued. The timing of the appearance of CD8+ cell anti-HIV activity directly correlated with the emergence of detectable virus levels. Maximal CNAR activity coincided with a decay in the kinetics of HIV replication. In addition, peak viral loads during treatment interruption were lower than pre-treatment virus levels (median reduction = 0.8 logs, p = 0.005) and CD4+ T cell counts were maintained for a 24-week period of follow-up. Conclusion  These results suggest that CNAR plays an important role in suppressing HIV replication in the setting of antiretroviral treatment interruption in HIV-infected individuals.     

Phenotypic characterization of CD8+ T cell populations in HIV disease and in anti-HIV immunity.

The CD8+ T cell population is believed to play an important role in the control of viral infection, both for suppression of viral replication and for cytotoxic activity against viral infected cells. Elevated numbers of CD8+ T cells have been demonstrated in HIV infection, and CD8+ cytotoxic T cell (CTL) activity is associated with the early, asymptomatic stage of disease. We investigated the phenotypic characteristics of the CD8 population, in whole blood, in HIV disease and determined the predominant CD8+ subpopulation involved in anti-HIV CTL activity. We found that CD8+ T cells co-expressing markers of activation (HLA-DR), memory (CD45RO, CD29), and cytotoxic activity (S6F1) were significantly elevated in the early stages of disease, while the numbers of naive (CD45RA) cells remained unchanged. Progression to AIDS resulted in an overall loss of absolute CD8+ T cells, though the percentages of CD8+ HLA-DR+ and CD8+ S6F1+ remained elevated. In contrast to patients in the late stages of disease, anti-HIVgag CTL activity, following in vitro stimulation, was present in most HIV+ asymptomatic subjects and was associated with an expansion of CD8+ HLA-DR+ and CD8+ CD45RO+ cells. The absence of CTL activity was associated with a reduced ability of these populations to expand in vitro and with a significant loss of peripheral CD4+ T cells, independent of clinical stage. We suggest that CD8+ expressing HLA-DR+ CD45RO+ and S6F1+ play an important role in anti-HIV cytotoxicity.     

Changes in natural immunity during the course of HIV-1 infection.

The role of natural killer (NK) and lymphokine-activated killer (LAK) cell-mediated cytotoxicity in AIDS has yet to be established. The objective of this study was to determine inducible LAK cell responses at different stages of HIV-1 infection, and specifically to establish the participation of CD8 lymphocytes in these responses. Peripheral blood lymphocytes (PBL) were isolated from healthy seronegative (CDC-0) subjects and HIV-1+ individuals who were clinically asymptomatic (Centre for Disease Control group 2, CDC-2) or symptomatic (CDC-4) with regard to secondary opportunistic infection (OI). LAK cells were generated upon incubation of PBL with IL-2 and their cytolysis of K562 and U-937 targets was determined using chromium release assays. The role of CD8+ lymphocytes as progenitors and effectors of these LAK cell responses was determined by immunomagnetic depletion of CD8+ cells from precursor PBL and LAK cells, respectively. LAK cell-mediated cytotoxicities in HIV-1-infected individuals were reduced compared with seronegative controls without any corresponding changes in the relative proportions of CD56+ (NK) cells among groups. Depletions of CD8+ subsets from either PBL or LAK cells dramatically reduced total LAK cytotoxic responses and LAK activities per unit CD56+ cell in the OI-/CDC-2 seropositive population. No corresponding changes in LAK activities in seronegative control or HIV+/OI+/CDC-4 groups were observed. Levels of LAK activity against K562 targets in CDC-0/HIV- and CDC-4/HIV+ groups correlated with the percentage of CD56+ LAK cells; corresponding LAK activity in the CDC-2/HIV+ group correlated with the percentage of both CD56+ and CD8+ subsets. These findings suggest that adaptive changes in non-MHC restricted cytotoxic responses occur in HIV-1 individuals at early stages post-HIV infection, before the onset of opportunistic infection.     

Antigen-specific beta-chemokine production and CD8 T-cell noncytotoxic antiviral activity in HIV-2-infected individuals

Human immunodeficiency virus-2 (HIV-2) is less pathogenic than HIV-1, and the disease progression in HIV-2-infected individuals seems to be similar to that seen in HIV-1-infected long-term nonprogressors. Cell-mediated immune responses and the production of noncytotoxic CD8+ T-cell antiviral factors (CAF) and beta-chemokines have been correlated to protection against HIV-1 and associated with asymptomatic infection and slower disease progression. We investigated the antigen-induced beta-chemokine production in HIV-2-infected patients living in Sweden and in Guinea-Bissau. We also compared in vitro CD8+ T-cell-mediated noncytotoxic antiviral activity against beta-chemokine-sensitive R5 virus (HIV-1Bal) and beta-chemokine-insensitive X4 virus (HIV-1IIIB) in HIV-2-infected patients with that in HIV-1-infected patients. HIV-2-specific beta-chemokine production was demonstrated in a majority of the HIV-2-infected subjects. CD8+ T cells of both HIV-1 and HIV-2-infected individuals suppressed R5 virus replication in vitro in a similar manner, while the inhibition of X4 virus replication seemed to be more frequent and of a higher magnitude among HIV-2-infected patients compared to HIV-1-infected subjects. Taken together, our results indicate that the production of CD8+ T-cell noncytotoxic antiviral factors may contribute to the low transmission of the virus and slower disease progression in HIV-2-infected patients.     

Evidence for circulating activated cytotoxic T cells in HIV-infected subjects before the onset of opportunistic infections

The activity of both cytotoxic T lymphocyte (CTL) and natural killer (NK) cells were measured cross-sectionally in 43 subjects seropositive for HIV, in 27 HIV- blood donors and in 24 HIV- persons from the Outpatients Clinic for sexually transmitted diseases. CTL activity was evaluated using the HL-60 cells coated with OKT3 as the targets and freshly separated peripheral blood lymphocytes as the effectors. In 20 out of 43 HIV+ subjects, CTL activity was significantly enhanced in comparison to the HIV- subjects. This lytic activity correlated positively with the percentages of CD3+ HLA-DR+, of CD8+ CR3- and of CD57+ CD16- lymphocytes, and was greatly reduced after elimination of CD8+, of HLA-DR+ or of CD57+ cells. The median CTL activity seemed to increase from CDC group II to CDC group IV (Centers for Disease Control classification), but to return back to control levels in those patients with a history of opportunistic infections. NK function in HIV+ subjects was not significantly different from that in the blood donors. In seropositive patients, NK activity correlated positively with the percentages of both CD16+ CD57+ and of CD8+ CR3+ cells and was strongly diminished after elimination of CD16+ or of CD57+ cells. There was no significant change in NK function according to the clinical stage. The data show that circulating CD8+ HLA-DR+ CD57+ T cells in HIV+ subjects are activated cytotoxic T cells and point to progressive (over) activation of this T cell compartment until the onset of opportunistic infections.     

Neutralizing antibodies as a prognostic indicator in the progression of acquired immune deficiency syndrome (AIDS)-related disorders: A double-blind study

A double-blind longitudinal study for the presence of human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies (NAb) in the sera of 36 patients with acquired immune deficiency syndrome (AIDS), 149 prodromal homosexual subjects, and 33 heterosexual subjects has been carried out. All AIDS patients and 68% of prodromal homosexual subjects (101/149) were found to be HIV-1 antibody positive by Western blot assay. All heterosexual subjects were HIV-1 antibody negative. Neutralizing antibody(s) was determined by testing the protective activity of sera against HIV-1 infection of human T-cell line H9. Study subjects were divided into NAb(+) (antibody titer, >1:40) and NAb(–) (antibody titer, <1:40) groups. During the 24-month observation period 2 of 80 (3%) HIV-1(+) NAb(+) individuals progressed to AIDS and died, as compared to 5 of 21 (24%) of HIV-1(+) NAb(–) subjects who progressed to AIDS. Similarly, among the NAb(+) AIDS patients 8 of 23 (35%) died, while 10 of 13 (77%) of the NAb(–) patients died during the course of the study. In addition, the absence or reduction of HIV-1 p17 and p24 antibodies directed against HIV-1 antigens as well as the low titer or absence of NAb appears to be closely related to the clinical progression of the disease. These studies suggest that a decrease in the virus neutralization capacity of the sera and a decrease or complete loss of HIV-1 p17 and p24 antibodies may be useful as prognostic indicators for the progression of disease in HIV-1-seropositive patients.     

中国HIV-1 B'/C亚型感染者对异体病毒中和作用与疾病进展关系研究

目的 探讨中国HIV-1 B'/C亚型感染者对异体病毒中和作用与疾病进展的关系.方法 根据CD4 T淋巴细胞数量和有尤临床症状将HIV-1 B'/C亚型感染者分为HIV慢性感染组和AIDS组.将HIV-1感染者血清稀释(1/10～1/320)后,与在基因结构特点上同源性很低的3株HIV-1作用,以检测其中和作用.同时以正常人血清加病毒悬液为对照孔,能够抑制对照孔50%病毒复制的血清为中和作用阳性.将某个HIV-1感染者血浆能够中和异体病毒的个数占3个异体病毒的百分率定义为HIV-1感染者中和异体病毒的宽度;将某个HIV-1感染者血浆中和3个异体病毒抗体滴度的几何平均滴度定义为HIV-1感染者中和异体病毒的强度.结果 HIV-1慢性感染组与AIDS组之间中和异体病毒的宽度和强度差异有统计学意义,HIV-1慢性感染组显著高于AIDS组.HIV-1慢性感染组中和异体病毒的宽度和强度与病毒载量呈正相关,而AIDS组巾和异体病毒的宽度和强度与病毒载量没有显著的相关性.HIV-1慢性感染组和AIDS组中和异体病毒的宽度和强度与CD4 T淋巴细胞数均没有显著的相关性.结论 中国HIV-1B'/C亚型感染者不同疾病进展阶段针对异体病毒中和作用能力不同,HIV慢性感染组显著高于AIDS组,当疾病进展到AIDS期时,失去对异体病毒的中和作用,提示针对异体病毒的中和抗体与疾病进程有关.     

Comprehensive analyses of a unique HIV-1-infected nonprogressor reveal a complex association of immunobiological mechanisms in the context of replication-incompetent infection

We recently demonstrated that a unique HIV-1-infected nonprogressor was infected with a nonevolving replication-incompetent HIV-1 strain, showing a total absence of viral evolution in vivo. Potent immune responses against HIV-1 were observed in his PBMC, despite an apparent lack of viral replication for at least 8 years. His PBMC resisted superinfection with CCR5, CXCR4, and dual-tropic HIV-1 strains, although highly purified CD4+ T cells supported infection, but without any visible cytopathic effect. Potent noncytolytic CD8+ T cell antiviral activity was shown to protect his PBMC from productive infection. This activity was not mediated by several known chemokines or IFN-gamma, which were produced at high levels after PHA activation of his CD8+ T cells, indicating the action of other CAF-like CD8 factors. This antiviral activity was a memory response, induced by HIV-specific stimulation to similar levels observed by PHA stimulation, but absent in ex vivo resting T cells. Immunological mechanisms associated with this antiviral suppressive activity included vigorous Gag-specific helper T cell proliferative responses and high-level IFN-gamma release by both CD4 and CD8 T cells. These responses were broadly directed against multiple Gag epitopes, both previously reported and some novel epitopes. Strong HIV-specific helper T cell function was also associated with strong neutralizing antibodies. Understanding how to induce these protective immune responses in other individuals could provide a major step forward in the design of effective immunotherapies or vaccines against HIV infection.     

Human immunodeficiency virus (HIV) gag antigen-specific T-helper and granule-dependent CD8 T-cell activities in exposed but uninfected heterosexual partners of HIV type 1-infected individuals in North India

Repeated exposure to human immunodeficiency virus (HIV) does not always result in HIV infection, and several cohorts of HIV-exposed but uninfected (EU) individuals have been described. We studied T-helper and granule-dependent cytotoxic T-lymphocyte (CTL) activities in a group of 30 EU partners of HIV type 1 (HIV-1)-infected individuals. HIV-1-specific helper-T-cell activity was studied by measuring the levels of interleukin 2 (IL-2) produced by peripheral blood mononuclear cells (PBMCs) and the granule-dependent CTL activity by measuring the intracellular levels of perforin and granzyme B expression in CD8+ T cells after stimulation with gag p24 antigen. Elevated IL-2 production by PBMCs after p24 stimulation occurred in EU individuals. The levels of perforin and granzyme B expression in CD8+ T cells were also higher among EU individuals than among healthy controls. HIV-specific helper-T-cell and granule-dependent CTL activities inversely correlated with the time since the last unprotected sexual exposure in these individuals. In our cohort, activation of T-helper and granule-dependent CTL activities against HIV might be due to unprotected sexual contact. These results indicate that HIV-1-specific T-cell responses could play a role in protection against acquiring infection in this cohort of EU individuals.     

Anti-viral activity of human antithrombin III

Soluble inhibitory factors produced by CD8+ T-cells have been shown to inhibit HIV-1 replication and may play a critical role in vivo in anti-viral host defense. CD8+ T-cell-modified antithrombin III (ATIII) accounts for some of the described CD8+ T-cell anti-viral activity. We demonstrate that CD4+ T-cells, CD8+ T-cells, and natural killer cells react to an ATIII gradient by cell migration. Furthermore, exogenously added ATIII induced a G-protein-coupled signal transduction process in CD4+ T-cells and inhibited TNF-alpha-induced NF-kappaB activation. Heat and/or heparin treatment prior to the anti-viral inhibition test increased the anti-HIV activity up to 1000-fold. Our data indicate that anti-viral inactive ATIII can be activated having promising anti-viral properties as complementary candidate for the treatment of HIV infection.     

Expression of perforin on HIV-1-specific CD8+ lymphocytes after immunization with a gp120-depleted, whole-killed HIV-1 immunogen.

We examined HIV-1 antigen specific intracellular expression of perforin on CD4+ and CD8+ lymphocytes in subjects with chronic HIV-1 infection on antiviral drug therapy after immunization with a gp120-depleted, whole killed HIV-1 immunogen (inactivated, gp120-depleted HIV-1 in IFA, REMUNE). Based upon previous results, we hypothesized that the restoration of adequate T helper immune responses by vaccination against HIV-1 could result in the augmentation of CD8+ lymphocyte immune responses measured as perforin expression. In the current study we observed an increase in the frequency of perforin in CD8+ lymphocytes in HIV infected individuals immunized with a gp120-depleted HIV-1 immunogen while on antiviral drug therapy. Furthermore, the frequency of HIV-specific CD8+ perforin expressing cells correlated with the T helper immune response as measured by the lymphocyte proliferative response (LPR). The induction of such responses with immunization may have direct antiviral consequences and is being studied in ongoing clinical trials.     

Effect of IL-2 Therapy on CD8+ Cell Noncytotoxic Anti-HIV Response During Primary HIV-1 Infection

Early treatment intervention during human immunodeficiency virus (HIV) infection is a strategy aimed to preserve and/or enhance the developing anti-HIV immune responses. We report the effect of highly active antiretroviral therapy (HAART) combined with intermittent subcutaneous doses of Interleukin 2 (IL-2) on CD8(+) cell noncytotoxic anti-HIV responses (CNAR), as well as on viral loads and CD4(+) cell/CD8(+) cell numbers in subjects with primary HIV-1 infection. Twenty-four patients received HAART, 24 received a combination of HAART plus IL-2, and 12 elected no-therapy. In comparison to HAART alone, IL-2 treatment led to significant increases in CD4(+) cell numbers through week 48 of the study. No effect was observed on viral loads or the CD8(+) cell population. The first cycle of IL-2 enhanced CNAR; later cycles showed no substantial effect. This study suggests that HAART combined with IL-2 could provide an immunologic benefit in the treatment of early HIV infection.     

Immune responses to fractionated cytomegalovirus (CMV) antigens after HIV infection. Loss of cellular and humoral reactivity to antigens recognized by HIV-, CMV+ individuals.

In order to delineate the molecular pathogenesis of the increased susceptibility to CMV disease in HIV infection, the patterns of antigen responsiveness in HIV-infected and non-infected individuals were investigated. CMV was fractionated by SDS-PAGE and electroblotted onto nitrocellulose. Lymphoproliferative responses of healthy HIV-, CMV+ individuals and HIV+, CMV+ asymptomatic patients to a whole CMV antigen preparation and to 20 fractions of nitrocellulose-bound CMV were then compared. Three fractions of approximate molecular weight of 130-165, 65-75, and 55-65 kD appeared to contain the major T cell stimulating antigens for HIV-, CMV+ individuals. A statistically significant depression of responses to fractions containing antigens in the ranges of 130-165 kD and 55-65 kD but not to whole CMV was seen in HIV+ individuals compared with controls. In healthy controls, the sum of the proliferative responses as measured by 3H-thymidine uptake to these three major fractions was approximately equal to the response to a whole CMV antigen preparation, whereas it was less than half of this response in five out of six HIV+ subjects. When antibody activities to CMV antigens were analysed by immunoblotting of sera from the two subject groups and also sera of ARC and AIDS patients, a selective loss of reactivity was revealed in 10 out of 19 HIV+ subjects to a band of 26-28 kD whereas all 15 HIV-, CMV+ controls recognized this band. Serum IgG and IgM values were both significantly higher in HIV+ individuals than in controls. These findings suggest that specific lesions in the repertoire of immune responsiveness to CMV antigens occur in HIV+ individuals.     

CD8+ cell lines isolated from HIV-1-infected children have potent soluble HIV-1 inhibitory activity that differs from beta-chemokines

CD8+ cells from human immunodeficiency virus type 1 (HIV-1) infected individuals have been shown to suppress HIV-1 replication both through a major histocompatibility complex (MHC)-restricted cytolytic pathway as well as through a noncytolytic pathway mediated through soluble factors. To characterize this soluble activity and its potential role in disease progression further, we studied the HIV-1 inhibition by supernatants derived from herpesvirus saimiri-transformed CD8+ cells isolated from infected children. Three of the six CD8+ cell lines derived had a phenotype consistent with an unusual natural killer (NK) cells phenotype with low CD3, high CD56, and low CD16. Supernatants from some of the cell lines derived from children with rapid progression as well as long-term nonprogressors exhibited broad HIV-1-inhibitory activity in primary CD4+ cells as well as in primary macrophages. In contrast to a cocktail of beta-chemokines, the supernatants inhibited T-tropic as well as M-tropic viruses, efficiently inhibited infection in primary macrophages, and inhibited HIV-1 activation in the chronically infected U1 cell line. The HIV-1-inhibitory activity was heat stable and active over a broad pH range. Fractionation of the supernatant by size and ion exchange chromatography demonstrated activity in the complete absence of RANTES as well as interferons-alpha, beta, and gamma and in a size range of less than 10 kD and greater than 3 kD. CD8+ cell supernatants contain additional unidentified factors that have anti-HIV activity to account for this broad phenomenon.     

Natural controlled HIV infection: preserved HIV-specific immunity despite undetectable replication competent virus

Long-term non-progressive HIV infection, characterized by low but detectable viral load and stable CD4 counts in the absence of antiviral therapy, is observed in about 5% of HIV-infected patients. Here we identified four therapy na?ve individuals who are strongly seropositive for HIV-1 but who lack evidence of detectable HIV p24 antigen, plasma RNA, and proviral DNA in routine diagnostic testing. With an ultrasensitive PCR, we established that frequencies of pol proviral DNA sequences were as low as 0.2-0.5 copies/10(6) PBMC. HIV could not be isolated using up to 30x10(6) patient PBMC. One individual was heterozygous for CCR5 Delta32, but CCR5 expression on CD4+ T cells was normal to high in all four individuals. In vitro R5 and X4 HIV-1 susceptibility of CD8-depleted PBMC of all study subjects was significantly lower than the susceptibility of CD8-depleted PBMC of healthy blood donors. All individuals expressed protective HLA-B*58s alleles and showed evidence of HIV-specific cellular immunity either by staining with HLA-B*57 tetramers folded with an HIV RT or gag peptide or after stimulation with HIV-1 p24 gag, RT, or nef peptides in ELIspot analysis. HIV-specific CD4+ T helper cells were demonstrated by proliferation of CD4+ T cells and intracellular staining for IL-2 and IFNgamma after stimulation with an HIV-gag peptide pool. Sera of all individuals showed antibody-mediated neutralization of both R5 and X4 HIV-1 variants. These data implicate that very low-level antigen exposure is sufficient for sustained HIV-specific immunity and suggest the possibility of a multi-factorial control of HIV infection.     

T cells expressing high levels of non-major histocompatibility complex (MHC)-restricted cytotoxicity are present in early and late clinical phases of human immunodeficiency virus 1 (HIV-1) infection

Cytotoxic cells appear to play an important role in host defense against viral infection. In HIV-1 infection there is an expansion of the Leu7-positive lymphocyte population which is associated with cytotoxic activity. Since a form of non-MHC-restricted T-cell cytotoxicity [lectin-dependent cell cytotoxicity (LDCC)] has been reported to be mediated by CD3+Leu7+ cells, we evaluated LDCC and Leu7-positive lymphocyte populations in HIV-1-infected subjects and healthy controls. Both LDCC and percentages of Leu7+CD3+ and Leu7+CD2+ cells were increased in HIV-1-infected individuals as compared to controls. However, the CD3+Leu7+ lymphocyte population was increased to a greater degree than the CD8+Leu7+ population and a minor Leu7+ cell population (Leu7+CD4+) was expanded in the early stages of infection. Lectin-dependent cell cytotoxicity was positively correlated with the percentages of Leu7+CD3+ cells. Thus T-cells with the capacity to mediate high levels of non-MHC-restricted cytotoxicity are present in increased proportions in HIV-1-infected individuals and persist in advanced disease. Further studies are required to see if these cells participate in HIV-specific cytotoxicity or reflect an aberrant, ineffective, or immunologically detrimental response to the virus.     

Anti-neutrophil cytoplasmic autoantibodies in patients with symptomatic HIV infection.

Antibodies against cytoplasmic antigens of neutrophils, producing perinuclear (p-ANCA) as well as cytoplasmic staining with central accentuation (c-ANCA), have been described in non-HIV-infected patients with specific pathology such as glomerulonephritis and vasculitis. Here, we report on a patient with a vasculitis-like syndrome and a positive ANCA-test who appeared to be infected by HIV. Further analysis revealed that ANCA, p-ANCA as well as c-ANCA without central accentuation can be demonstrated in the serum of HIV+ individuals. In a cross-sectional study on individuals in different stages of HIV infection, we found that the occurrence of ANCA was limited to the symptomatic stages of HIV infection: p-ANCA was found in one out of 10 ARC patients and in two out of 11 AIDS patients with malignancies (AIDS-MAL), but not in AIDS patients with opportunistic infections (AIDS-OI). c-ANCA was found in four of the ARC patients, in two of the 14 AIDS-OI patients and in two AIDS-MAL patients. The presence of ANCA was not related to the degree of hypergammaglobulinaemia nor to specific symptomatology. ANCA containing sera from HIV+ individuals did not react with HEp2 cells nor with cytoplasmic antigens of lymphocytes, natural killer (NK) cells or eosinophils. Five out of the 11 (two p-ANCA and three c-ANCA) sera reacted weakly with cytoplasmic antigens of monocytes. All sera reacted with karyoplasts but not with cytoplasts prepared from neutrophils. These results suggest that HIV-ANCA might be directed against myeloid cell-specific granule constituents. However, sandwich-ELISAs with MoAbs against granule antigens that are frequently the target antigens of ANCA in HIV- individuals were negative. Also immunoprecipitation and immunoblotting, using lysates of neutrophil granules, did not allow further identification of the target antigens of HIV-ANCA.     

Function of NKT cells, potential anti-HIV effector cells, are improved by beginning HAART during acute HIV-1 infection

NKT cells are a subset of lymphocytes that share features of T cells and NK cells and bridge the innate and adaptive immune responses. They are able to be infected by HIV, but their function in HIV-infected individuals is not known. NKT cell percentage and function was measured in individuals with acute HIV infection before and 1 year into highly active anti-retroviral therapy (HAART). This study demonstrates that percentages of both CD161+ NKT cells and CD161+, CD4+ NKT cells decline within the first few months after HIV-1 infection, but initiating therapy during the acute infection period can prevent a further decline in these NKT cell subsets during the first year. NKT cell function is also impaired during early HIV infection, but significantly improved by effective treatment with HAART. Finally, preservation of NKT cell function may be important in HIV-infected individuals, as NKT cells display an anti-HIV-1 activity in vitro, mediated by IFN-gamma secretion.