Pathogenic and protective correlates of T cell proliferation in AIDS. HNRC Group. HIV Neurobehavioral Research Center.

Abstract

To investigate the association of antigen specific CD4 T cell activation with HIV disease progression and AIDS-related central nervous system damage, T cell proliferation responses to HIV, CMV, and HSV were evaluated in infected individuals. CD4 T cell loss and neurocognitive impairment were assessed at 6-mo intervals.Individuals with known times of seroconversion who responded to more HIV peptides were at greater risk of progressing to Ͻ 200 CD4 T cells ( P ϭ 0.04) and dying ( P ϭ 0.03) than those with responses to fewer peptides. A positive correlation (0.52) was seen between the breadth of the HIV proliferation response and HIV plasma RNA levels. Higher proliferation responses to CMV and HSV were also associated with more rapid CD4 loss ( P ϭ 0.05).HLA phenotyped individuals ( n ϭ 150) with two HLA-DR alleles associated with response to more HIV peptides and CMV (DR-2,5,w6,10) were less likely to develop neurocognitive ( P ϭ 0.002) and neurologic impairment ( P ϭ 0.04), but were not protected from CD4 loss and death. Thus, the ability to generate a greater T cell proliferation response to HIV and opportunistic herpes viruses may lead to resistance to central nervous system damage, but also risk of more rapid HIV disease progression. ( J. Clin. Invest. 1996. 98:731-740.)

Determination of antigen-specific memory/effector CD4+ T cell frequencies by flow cytometry: evidence for a novel, antigen-specific homeostatic mechanism in HIV-associated immunodeficiency.

“…Indeed, it might correlate (either positively or negatively) with overall immune damage in HIV disease, and therefore be predictive of clinical course. In this regard, it is interesting that Schrier et al (53,54) recently correlated relatively high CMV-induced T cell proliferative responses in HIVϩ subjects with decreased incidence of CMV disease, but more rapid overall progression of the HIV disease. Clearly, long-term prospective clinical studies will be required to formally test this hypothesis.…”

Effect of Combination Antiretroviral Therapy on T‐Cell Immunity in Acute Human Immunodeficiency Virus Type 1 Infection

“…HIV-1-specific responses, typically absent among patients at all disease stages [10,11,[27][28][29] except nonprogressive infection [21], are observed in the early-treated patients but remain impaired in the untreated group. Our results indicate that, as plasma viremia falls to levels that are nearly undetectable with treatment, the CD4 ϩ T cell-mediated HIV-1 Gag-specific Th cell response emerges, which can be sustained for at least 1 year, the duration of our observation.…”

Severe genital herpes infections in HIV-infected individuals with impaired herpes simplex virus-specific CD8+cytotoxic T lymphocyte responses

“…Recently, Schrier et al (28) suggested that HIVϩ patients were at a higher risk of HIV disease progression when higher proliferative responses to HSV and cytomegalovirus were present in bulk PBMC cultures. We found no correlation between CD4 ϩ lymphocyte counts and bulk proliferation to HSV in HIVϩ PBMC from HSV-seronegative ͑HSVϪ͒, HSV-seropositive ͑HSVϩ͒, and HIVϩ-HSV-seropositive ͑HSVϩHSVϩ͒ subjects were tested for proliferation in response to HSV-AG and PHA and the median values for SI, ⌬cpm ͑HSV-AG͒, and total cpm ͑PHA͒ with ranges are displayed.…”