Relation between HIV-2 proviral load and CD4+ lymphocyte count differs in monotypic and dual HIV infections

OBJECTIVE: To explore and compare the relations between proviral DNA load and CD4+ lymphocyte counts in both HIV-2 monotypic and HIV dual infection. STUDY DESIGN/METHODS: In Dakar, Senegal, where the HIV-1 and HIV-2 epidemics overlap, serum and peripheral blood mononuclear cell (PBMC) DNA samples were collected from registered female sex workers and hospitalized patients. Sera were evaluated for reactivity to antigens of HIV-1 and HIV-2 by immunoblot; dual reactivity was confirmed with recombinant envelope peptides for HIV-1 and HIV-2. These samples were then subjected to HIV-1 and HIV-2 proviral DNA polymerase chain reaction (PCR). To evaluate the HIV-2 cellular proviral DNA loads, a quantitative competitive PCR (QC-PCR) was developed using nested primers to amplify the gag region of HIV-2. This assay used an internal competitor generated by inserting 25 bp in the first-round PCR target sequence. T-lymphocyte subset counts were estimated by flow cytometry for both HIV-2 monotypic and dually infected persons. RESULTS: 35 HIV-2-infected and 33 dually seroreactive samples were evaluated in this study. The CD4+ lymphocyte counts were similar in both groups, with mean values of 449 +/- 390 cells/mm3 for the HIV-2 monotypic infected persons and 476 +/- 308 cells/mm3 among the dually infected persons. However, the median proviral loads differed significantly, with those in the HIV-2 group ranging from 63.2 to 669.8 copies/10(5) CD4+ cells and demonstrating an inverse correlation with CD4+ lymphocyte count. The HIV dually infected persons showed less variation in viral load, ranging from 9.9 to 43.3 copies/10(5) CD4+ cells. Among the HIV dually infected persons, low HIV-2 proviral load was correlated with low CD4+ lymphocyte counts. CONCLUSIONS: The HIV-2 proviral loads in HIV dually infected persons were significantly lower than those in HIV-2 monotypically infected individuals (P < .0001), despite comparable CD4+ lymphocyte counts. These results suggest that different HIV-2 proviral dynamics prevail in HIV dual infection.     

Effect of HIV-1 infection on lymphocyte proliferation in gut-associated lymphoid tissue

OBJECTIVE: To determine the change in the percentage of proliferative and activated lymphocytes in gut-associated lymphoid tissue (GALT) in HIV-1-infected subjects compared with that in uninfected controls. METHODS: We measured the percentage of proliferative (Ki-67+) and activated (CD-69+, HLA-DR+, CD45RO+) lymphocytes from GALT and peripheral blood in chronically HIV-1-infected (12) and uninfected (9) individuals. RESULTS: The percentage of proliferative GALT CD4+ T cells was increased in HIV-1-infected control subjects compared with that in uninfected controls (p <.007). Based on immunohistochemical staining, proliferative T cells were principally located in the parafollicular area surrounding lymphoid aggregates. The percentage of activated GALT lymphocytes, however, was not significantly different in HIV-1-infected individuals, whereas it was significantly increased in the peripheral blood of HIV-1-infected individuals. The percentage of peripheral blood lymphocytes trafficking to the intestine was also not significantly different in HIV-1-infected individuals compared with that in uninfected controls. CONCLUSIONS: CD4+ T cell proliferation in GALT is increased in HIV-1 infection without a significant alteration in the percentage of peripheral blood T cells trafficking to the gastrointestinal mucosa.     

Natural killer cell-mediated lysis of T cell lines chronically infected with HIV-1.

The susceptibility of HIV-1-infected CD4+ T cell lines to natural killer (NK) cell-mediated lysis was examined. Non-adherent peripheral blood mononuclear cells (PBMC) of healthy adults lysed HUT cells chronically infected with the IIIB or WMJ1 strains of HIV-1 to a significantly greater extent than uninfected HUT cells. In contrast, Sup-T1 cells chronically infected with these two strains of HIV-1 were not lysed to a greater extent than uninfected Sup-T1 cells. Clone A1.25-infected Sup-T1 (A1.25/Sup-T1), derived from IIIB-infected Sup-T1 cells (IIIB/Sup-T1), were susceptible to non-adherent PBMC-mediated lysis, as were A1.25-infected HUT cells (A1.25/HUT). When non-adherent PBMC were depleted of CD16 (Leu-11b)+ NK cells by treatment with anti-Leu-11b plus C, lysis of HIV-1-infected HUT or Sup-T1 cells was reduced to low levels, indicating that the lysis was mediated by NK cells. Expression of HIV antigens on these target cells did not correlate with their susceptibility to NK cell-mediated lysis. Depletion of interferon-alpha (IFN-alpha) producing HLA-DR+ cells from non-adherent PBMC had no effect on the magnitude of NK cell-mediated lysis of IIIB or WMJ1-infected HUT cells. In contrast, lysis of A1.25/Sup-T1 or A1.25/HUT cells required the presence of HLA-DR+ cells. IFN-alpha production appeared to be required for NK cell-mediated lysis of A1.25/Sup-T1 or A1.25/HUT cells, while lysis of HUT cells infected with the WMJ1 or IIIB strains of HIV-1 was IFN-alpha independent. These results indicate considerable variability in the susceptibility of different HIV-1 infected T cell lines to NK cell-mediated lysis and suggest the existence of alternative mechanisms of activation of NK cells for lysis of HIV-1-infected T cell lines.     

HLA-B宽特异性抗原Bw4与HIV-1感染者疾病进展关系的研究

目的 对我国HIV-1感染者HLA-B基因不同基因型(Bw4、Bw6)的分布及其与疾病进展相关性进行研究,探讨HIA-Bw4基因在HIV-1疾病进程中的作用.方法 应用高分辨率HLA分型方法 对340名HIV-1感染者和69名健康对照进行HLA-B位点的等位基因分型,确定Bw4和Bw6特异性分布,分析HLA-B Bw4和Bw6特异性与感染者CD4+T细胞计数和血浆病毒载量的相关性.结果 在HIV-1感染者人群共检测到65种HLA-B等位基因,Bw4携带者(Bw4Bw4纯合子和Bw4Bw6杂合子)相对Bw6纯合子具有更高的CD4+T细胞计数(P=0.004)和更低的病毒载量(P=0.003).与Bw4纯合子相比,Bw4Bw6杂合子的CD4+T细胞计数差异无统计学意义,但病毒载量更低(P=0.037).在CD4+T细胞数小于500个/μl组中,Bw4Bw6杂合子的百分比显著低于CD4+T细胞数大于500个/μl组(P=0.0002),而Bw6纯合子的百分比则显著高于CD4+T细胞数大于500个/μl组(χ2检验,P<0.0001).结论 HLA-Bw4对宿主感染HIV-1后,从病毒载量分析可能具有一定的保护性作用,其保护机制值得进一步深入研究.     

Enhancement of natural killer cell activation and antibody-dependent cellular cytotoxicity by interferon-alpha and interleukin-12 in vaginal mucosae Sivmac251-infected Macaca fascicularis

We studied the innate immune system of Cynomolgus monkeys (Macaca fascicularis) experimentally infected via the vaginal mucosae with a virulent simian immunodeficiency virus isolate SIVmac251. Animals were evaluated for their natural killer (NK) cell activity, and for their antibody-dependent cellular cytotoxicity. NK cells from SIVmac251-infected macaques show impaired NK cell activity compared to cells from uninfected animals. Subsequent treatment of NK cells with interferon-a (IFN-alpha) or interleukin-12 (IL-12) alone partially restored the NK activity. However, either treatment of NK cells with both IFN-alpha and IL-12 completely reversed the impairment of cytotoxicity induced by simian immunodeficiency virus (SIV) infection. Incubation of NK cells from infected but not from uninfected monkeys with IFN-alpha and IL-12 for 8 days increased the percentage of CD16+/CD56+ cells twofold to five-fold and enhanced antibody-dependent cellular cytotoxicity (ADCC) activity. Thus IFN-alpha and IL-12 greatly enhance both the NK cell and ADCC activities of peripheral blood cells from SIVmac251-infected animals and increase the number of NK cells in longer term culture. The combined effect of IFN-alpha and IL-12 in enhancing NK cell activity may provide a novel therapeutic approach for the restoration of depressed NK cell activity observed in human immunodeficiency virus (HIV)-infected patients.     

CD4+ T cell targeting of human immunodeficiency virus type 1 (HIV-1) peptide sequences present in vivo during chronic, progressive HIV-1 disease

We previously detected HIV-1 Gag-specific CD4+ T cells recognizing reference strain viral epitopes in subjects with progressive, chronic infection. To test whether these CD4+ T cells persist in vivo by failing to recognize autologous HIV-1 epitopes, we compared autologous plasma HIV-1 p24 nucleotide sequences with targeted HXB.2 strain Gag p24 CD4+ T cell epitopes in nine chronically infected, untreated subjects. In five responding subjects, 10 of 26 HXB.2 strain p24 peptides targeted by CD4+ T cells exactly matched autologous plasma viral sequences. Four subjects with plasma viral loads >100,000 copies/mL had no measurable p24-specific CD4+ T cell responses despite carrying HIV-1 strains that matched HXB.2 sequences at predicted epitopes. These results show that HIV-1-specific CD4+ T cells can persist in chronic HIV-1 infection despite recognition of epitopes present in vivo. However, with high-level in vivo HIV-1 replication, CD4+ T cells targeting autologous HIV-1 may be non-responsive or absent.     

Early markers of HIV-1 disease progression in a prospective cohort of seroconverters in Bangkok, Thailand: implications for vaccine trials

BACKGROUND: Some candidate HIV-1 vaccines may not prevent HIV-1 infection but may alter the course of disease. Surrogate endpoints based on early laboratory makers in HIV-1-infected persons who are antiretroviral therapy (ART)-naive will be useful for evaluating vaccine efficacy in slowing disease progression (VEp). We examined pretreatment HIV-1 viral loads and CD4 cell counts in recent HIV-1 seroconverters to inform selection of these endpoints. METHODS: We studied 130 newly HIV-1-infected injection drug users identified from a prospective cohort of initially uninfected persons in Bangkok during 1995 through 1998. We analyzed trends in HIV-1 viral loads and CD4 cell counts as well as progression to the surrogate endpoint, defined as 2 consecutive CD4 cell counts of fewer than 350 cells/mm, during 24 months after the first HIV-1 seropositive (FP) visit. RESULTS: Median HIV-1 RNA copies/mL with interquartile ranges were 43,693 (14,320-94,767) at the FP visit, 46,924 (16,273-104,314) at 6 months, 28,446 (11,292-54,325) at 12 months, and 18,080 (8713-54,059) at 18 months. HIV-1 viral loads at the FP visit and at 18 months were positively correlated (r = 0.53, P < 0.0001). Of 130 participants, 12% reached the surrogate endpoint by 6 months, 16% by 12 months, and 27% by 18 months. In Cox regression analyses, HIV-1 viral loads of more than 50,000 copies/mL at the FP visit (hazard ratio [HR] = 2.3, 95% confidence interval [CI]: 1.1-4.8) and first CD4 cell count of 500 or fewer cells/mm (HR = 7.6, 95% CI: 3.2-17.6) were independently associated with faster progression to the surrogate endpoint. CONCLUSIONS: Participants with high HIV-1 RNA levels and low CD4 cell counts close to the time of seroconversion were more likely to experience early immunologic progression. Approximately one quarter of seroconverters reached the surrogate immunologic endpoint within 18 months of their FP visit and before starting ART, suggesting the utility of this endpoint for analyses of VEp in some ongoing and planned HIV-1 vaccine efficacy trials.     

CD8+ T-cells suppress antigen-specific and allogeneic CD4+ T-cell responses to herpes simplex virus type 2-infected human dendritic cells

In this study we show that human dendritic cells (DC), productively infected with herpes simplex virus type 2 (HSV-2), activate CD8+ T cells that suppress antigen-specific and alloreactive CD4+ T cell expansion. Addition of CD8+ T cells to cultures of DC and CD4+ T cells blocked CD4+ T-cell proliferation in response to HSV-2-infected but not to uninfected DC. The effect was independent of prior HSV exposure or cognate MHC class I-restricted CD8-DC recognition as it was induced in CD8+ T cells from HSV-2-seronegative individuals and in mixed lymphocyte reactions using allogeneic DC. Both CD8+ CD25+ and CD8+ CD25- cells were shown to have suppressive capacities. The blood-derived CD25+ CD8+ T cells did not express Foxp3 mRNA but had a bona fide antiproliferative capacity in response to both uninfected and HSV-2-infected DC, whereas the CD25-CD8+ T cells were selectively activated to become antiproliferative by HSV-2-infected DC. These data imply that HSV infection of DC could modulate the immune response by activating CD8+ T cells.     

Enumeration of latently infected CD4+ T cells from HIV-1-infected patients using an HIV-1 antigen ELISPOT assay.

BACKGROUND: Latently infected resting CD4(+) T cells carrying replication-competent HIV-1 are present in naive, chronically infected individuals as well as in those who are receiving highly active antiretroviral therapy (HAART). These cells serve as a potential source of reactivation of viral replication and remain a major obstacle for the eradication of HIV-1. OBJECTIVES: The enzyme-linked immunospot (ELISPOT) assay was adapted to the detection and the enumeration of HIV-1 antigen-secreting cells at the single cell level. We applied this test to count latently HIV-1-infected CD4(+) T cells. STUDY DESIGN: Latently infected CD4(+) T cells were assessed in an in vitro model of HIV-1-infected resting CD4(+) T cells as well as in eighteen HAART-treated and in four HIV-1-infected untreated patients. Enriched CD4(+) T cells were cultured with or without antibodies against CD3 and CD28 T cell receptors and with irradiated peripheral blood mononuclear cells from HIV-1 seronegative individuals. At the term of the cell culture, CD4(+) T lymphocytes were tested using the HIV-1 antigen ELISPOT assay. RESULTS: In the experimental HIV-1 infection model, 5579+/-4190 CD4(+) T cells secreting HIV-1 antigen were enumerated after polyclonal activation. In contrast, only 15+/-6 HIV-1 immunospots were obtained from unstimulated T cells. In all patients tested, induced HIV-1 antigen-secreting cells were measured at a frequency of 55+/-108/10(6) CD4(+) T cells. CONCLUSION: As each immunospot represents one HIV-1 antigen-secreting cell, the HIV-1 ELISPOT assay is a powerful to enumerate circulating CD4(+) T lymphocytes latently infected with HIV-1.     

CXCR4 or CCR5 tropism of human immunodeficiency virus type 1 isolates does not determine the immunological milieu in patients responding to antiretroviral therapy

Here we address whether CCR5 or CXCR4 tropism of the predominant viral strain detected before or on combination antiretroviral therapy (ART) explains why some human immunodeficiency virus (HIV)-infected patients who begin ART with advanced HIV disease retain low interferon (IFN)-gamma responses, despite recovery of CD4(+) T cell counts. Tropism was determined by culture and confirmed by gp120 V3 loop sequence of multiple plasma samples in eight adult male patients who began treatment with <50 CD4(+) T cells/microL. Four patients had mixed infections, one had only R5 HIV, and three had only X4 HIV. Of these, two carried CCR5Delta32. Viral tropism was not related to CD4(+) T cell counts or HIV RNA levels. When immunological responses were monitored over several years, IFN-gamma responses to cytomegalovirus were below the median value of uninfected controls and similar in patients with R5, X4, or mixed infection. Interleukin-5 responses were low and plasma soluble CD30 levels were high at treatment onset, but resolved with control of HIV replication irrespective of HIV tropism. Levels of LAG-3 (lymphocyte activation gene-3 protein) were elevated in patients with uncontrolled HIV replication. Hence the immunological milieu did not reflect HIV tropism.     

Immunobiological characterization of <Emphasis Type="Italic">Graphidium strigosum</Emphasis> experimental infection in rabbits (<Emphasis Type="Italic">Oryctolagus cuniculus</Emphasis>)

An experimental infection of rabbits with a wild isolate of the gastric nematode Graphidium strigosum was carried out. Animals (3.5 months age) were infected with 1,000 L3 administered by bucoesophagic catheter (five rabbits) or kept as uninfected control group (five animals). The infection was maintained for 3 months. Along the experimental period, some parasitological, hematological and immunological parameters were determined. Prepatent period of the infection ranged from 30 to 38 days and, at necropsy, average adult helminth counts were 430.75 +/- 126.12. No significant variations were found in packed cell volume, leukocyte, and eosinophil counts along the experimental period. Infection elicited a clear serum-specific IgG response, estimated by ELISA, during patency. Pooled sera from the patent period of the infection recognized some soluble antigens, particularly, a 67-kDa protein. Experimentally infected animals did not show cross recognition between G. strigosum, Haemonchus contortus, and Teladorsagia circumcincta. However, Western blot analysis with hyperimmune sera against H. contortus raised in rabbits and lambs showed cross reactivity between this helminth species and G. strigosum.     

T cell receptor excision circles (TRECs) analysis during acute intrarectal infection of cynomolgus monkeys with pathogenic chimeric simian human immunodeficiency virus

Several studies have shown the importance of evaluating Recent Thymic Emigrants (RTEs) by quantification of T cell receptor-rearrangement excision circles (TRECs), as a measure of de novo T cell generation during human immunodeficiency virus-1 (HIV-1) infection. To determine whether acute viral infection may have an impact on TRECs, cynomolgus monkeys (Macaca fascicularis) were infected intrarectally with simian human immunodeficiency virus (SHIV) 89.6P(cy11) and the number of signal-joint (sj) TRECs was determined in purified CD4+ and CD8+ populations for up to 28 weeks post-infection. Four weeks after infection, TRECs levels significantly decreased in both CD3+ CD4+ and in CD3+ CD8+ T lymphocytes of infected monkeys, whereas they remained unchanged in uninfected animals. This reduction was followed by a progressive TRECs number recovery in CD3+ CD4+ T lymphocytes that positively correlated with changes in the levels of circulating CD3+ CD4+ T cells. In the CD3+ CD8+ T cell subset, TRECs number remained significantly low and inversely correlated with the increase in the percentages of CD3+ CD8+ T cells. These data suggest that SHIV89.6P(cy11) intrarectal infection of cynomolgus monkeys differently affects TRECs content in CD3+ CD4+ and CD3+ CD8+ T cell subsets.     

Are there gender and race differences in cellular immunity patterns over age in infected and uninfected children born to HIV-infected women?

This study investigated whether age-related patterns of immunologic markers in 1488 uninfected (9789 measurements) and 186 infected (3414 measurements) children differed by gender and race. CD4+, CD8+, and absolute lymphocytes by HIV infection status, gender, and race were assessed using linear mixed-effects natural cubic spline models, allowing for prematurity and maternal CD4+ cell count. In uninfected children, levels of all 3 markers peaked twice in the first few months of life, declining to adult levels by around 8 years of age; uninfected boys and uninfected black children had significantly reduced CD4+ and absolute lymphocyte counts; the gender difference was especially pronounced in black children. Infected children had substantially lower levels and distinctly different patterns; with, e.g., by age 6 months CD4+ cell counts nearly 1200 per mm3 lower than in uninfected infants. Levels also significantly differed by gender and race for infected children, although for gender in the opposite direction. The gender and race differences in CD4+ levels were not explained by a general lymphocytosis nor were they confounded by treatment. These substantial differences in immunologic markers may reflect underlying genetic influence on the cellular immune system and may have implications for clinical decisions about therapeutic management.     

Viral burden and disease progression in rhesus monkeys infected with chimeric simian-human immunodeficiency viruses

To determine the role of viral burden in simian-human immunodeficiency virus (SHIV)-induced disease, cellular provirus and plasma viral RNA levels were measured after inoculation of rhesus monkeys with four different SHIVs. These SHIVs included SHIV-HXBc2 and SHIV-89.6, constructed with env, tat, rev, and vpu derived from either cell line-passaged or primary patient isolates of human immunodeficiency virus type 1; the viral quasispecies SHIV-89.6P derived after in vivo passage of SHIV-89.6; and a molecular clone, SHIV-KB9, derived from SHIV-89.6P. SHIV-HXBc2 and SHIV-89.6 are nonpathogenic in rhesus monkeys; SHIV-89.6P and SHIV-KB9 cause rapid CD4(+) T cell depletion and an immunodeficiency syndrome. Relative SHIV provirus levels were highest during primary infection in monkeys infected with SHIV-89.6P, the virus that caused the most rapid and dramatic CD4(+) T cell depletion. However, by 10 weeks postinoculation, provirus levels were similar in monkeys infected with the pathogenic and nonpathogenic chimeric viruses. The virus infections that resulted in the highest peak and chronic viral RNA levels were the pathogenic viruses SHIV-89.6P and SHIV-KB9. SHIV-89. 6P uniformly caused rapid and profound CD4(+) T cell depletion and immunodeficiency. Infection with the SHIV-KB9 resulted in very low CD4(+) T cell counts without seroconversion in some monkeys and a substantial but less profound CD4(+) T cell depletion and rapid seroconversion in others. Surprisingly, the level of plasma viremia did not differ between SHIV-KB9-infected animals exhibiting these contrasting outcomes, suggesting that host factors may play an important role in AIDS virus pathogenesis.     

Perivascular macrophages in the neonatal macaque brain undergo massive necroptosis after simian immunodeficiency virus infection

We previously showed that rhesus macaques neonatally infected with simian immunodeficiency virus (SIV) do not develop SIV encephalitis (SIVE) and maintain low brain viral loads despite having similar plasma viral loads compared to SIV‐infected adults. We hypothesize that differences in myeloid cell populations that are the known target of SIV and HIV in the brain contribute to the lack of neonatal susceptibility to lentivirus‐induced encephalitis. Using immunohistochemistry and immunofluorescence microscopy, we examined the frontal cortices from uninfected and SIV‐infected infant and adult macaques (n = 8/ea) as well as adults with SIVE (n = 4) to determine differences in myeloid cell populations. The number of CD206+ brain perivascular macrophages (PVMs) was significantly greater in uninfected infants than in uninfected adults and was markedly lower in SIV‐infected infants while microglia numbers were unchanged across groups. CD206+ PVMs, which proliferate after infection in SIV‐infected adults, did not undergo proliferation in infants. While virtually all CD206+ cells in adults are also CD163+, infants have a distinct CD206 single‐positive population in addition to the double‐positive population commonly seen in adults. Notably, we found that more than 60% of these unique CD206+CD163? PVMs in SIV‐infected infants were positive for cleaved caspase‐3, an indicator of apoptosis, and that nearly 100% of this subset were concomitantly positive for the necroptosis marker receptor‐interacting protein kinase‐3 (RIP3). These findings show that distinct subpopulations of PVMs found in infants undergo programmed cell death instead of proliferation following SIV infection, which may lead to the absence of PVM‐dependent SIVE and the limited size of the virus reservoir in the infant brain.     

CD8+ T cells are the major lymphocyte subpopulation involved in the protective immune response to Toxoplasma gondii in mice.

The ability of the major T cell subsets to adoptively transfer resistance to T. gondii infection was studied. Spleen cells harvested from mice with a 3-month T. gondii infection and cells from uninfected mice were enriched for T cells by nylon/wool purification. Adoptive transfer of these cells from both groups of donor mice led to a significant increase in the survival of syngeneic recipient mice infected intraperitoneally with 20 T. gondii cysts. Increased survival was mediated particularly by CD4-depleted but also, to a lesser extent, CD8-depleted subpopulations. These results were confirmed in T cell reconstituted athymic nude mice. Unfractionated T cells from chronically infected donors produced a significant inhibition of cyst formation in the brains of recipient mice measured 10 weeks after infection compared with control mice. The inhibition of cyst formation was ablated by pretreating T cells with anti-CD8 antibody and complement, but not anti-CD4 antibody and complement. Mice receiving cells from infected donors produced an early increase in their IgG1 and IgG2a antibody titres compared with mice given cells from uninfected animals. The depletion of either CD8+ or CD4+ immune cells appeared to have little effect on the antibody responses in recipient mice and there was no correlation between antibody levels and immunity. The results indicate that CD8+ T lymphocytes from convalescent T. gondii-infected BALB/c mice are the principal mediators of resistance to T. gondii, although CD4+ T cells appear to be involved during the acute phase of infection.     

儿童急性淋巴细胞白血病化疗前后细胞免疫的变化及与人巨细胞病毒感染的关系

目的 探讨儿童急性淋巴细胞白血病(ALL)化疗前后细胞免疫的变化及与人巨细胞病毒(HCMV)感染的关系.方法 103例接受化疗的ALL患儿设为ALL组,34例健康儿童设为对照组,流式细胞术检测对照组、ALL组初治时、化疗结束时、化疗后3个月T细胞亚群.化疗结束时采用PCR检测HCMV病毒,并根据检测结果分为感染组和未感染组,对比分析两组T细胞亚群差异,多因素Logistic回归分析HCMV感染的影响因素.结果 ALL组(初治时)T细胞亚群CD3+、CD4+ 、CD8+、CD4 +/CD8+均低于对照组,差异有统计学意义(P ＜0.05);ALL组化疗前后CD3+、CD4+、CD4+/CD8+表现出先降低后升高的趋势,差异具有统计学意义(P＜0.05);化疗结束时共18例患者HCMV病毒检测为阳性,感染组化疗结束时CD3+、CD4+、CD4+/CD8+低于未感染组,差异有统计学意义(P＜0.05);多因素Logistic回归分析显示,疾病危险度是ALL患儿HCMV感染的危险因素(AOR=1.543,95％ CI:1.213～1.809,P=0.028),而CD3+、CD4+、CD4+/CD8+、最低PLT是HCMV感染的保护因素.结论 ALL自身以及化疗后细胞免疫功能降低,增加了HCMV感染风险,细胞免疫功能下降与HCMV感染可能互为因果.     

HIV-specific cellular immune responses are stimulated by structured treatment interruption in chronically HIV-1 infected Koreans

We evaluated the enhancing effect of structured treatment interruptions (STIs) on HIV-specific immunity in chronically HIV-1 infected Korean patients. A prospective case-control study was done with a total of 10 subjects for a period of 26 weeks. Six subjects were on STIs and four subjects were on continuous HAART for comparison. The STI subjects underwent four periods of STIs. For those on STIs, HAART was stopped at week 0 for two weeks, and resumed thereafter for six weeks. Viral load and CD4+/CD8+ T cells were measured by HIV RNA RT-PCR and flow cytometry, and HIV-specific immunity was measured by an ELISPOT assay. HIV-specific cytotoxic T cell immunity was more pronounced in the STI subjects than in the continuous HAART subjects after 26 weeks (p = 0.011). The difference in cytotoxic T cell response in the STI group was more prominent than in the continuous HAART group (p = 0.011). Viral load after 26 weeks was higher in the STI subjects than in the continuous HAART subjects (p = 0.008). An HIV-specific cellular immune response can be stimulated by STIs in chronically HIV-infected Koreans. A larger study is warranted in order to further characterize viral and immunological parameters of treatment with STIs in cases of chronic HIV infection.     

HIV-1感染者CD4+CD25nt/hiCD127lo调节性T细胞PD-1表达水平与疾病进展的关系

目的:阐明HIV-1感染者外周血中具有CD4+CD25nt/hiCD127lo特征的调节性T细胞(Treg)表面PD-1的表达水平与疾病进展的关系.方法:选取108名未经治疗的不同进展期的HIV-1感染者和27名健康人对照, 采集静脉血, 用Ficoll-Hypaque密度梯度离心法分离获得PBMC, 加入PerCP-CD4抗体、 FITC-CD25抗体、 PE-CD127抗体和APC-PD-1抗体, 经细胞表面四色染色、流式细胞术(FCM)分析Treg表面PD-1的表达;另将50 L全血加入Trucount绝对计数管, 采用Multitest CD3/CD8/CD45/CD4试剂盒检测CD4+T细胞绝对数;分离静脉血血浆, NucliSens EasyQ测定血浆HIV-1病毒载量;实验数据采用SPSS14.0 统计学软件分析处理.结果:HIV-1感染者Treg表面PD-1表达水平显著高于健康人(5.33%±2.24% vs 1.72%±0.65%, P<0.01);AIDS期(7.87%±2.23%)明显高于进展期(5.21%±1.72%, P<0.05)和新近感染者(3.22%±1.01%, P<0.05);HIV-1感染者Treg表面PD-1表达水平与血浆中的HIV-1病毒载量和CD4+T细胞绝对数密切相关.结论:首次证实HIV-1感染者外周血中Treg表面PD-1表达增加, 且表达水平与病程进展相关.该结果为进一步揭示HIV-1感染中Treg的效应机制、探索新的免疫治疗方案提供了理论及实验依据.