Immunological and virological markers in individuals progressing from seroconversion to AIDS.
Six men were selected from a large cohort of homosexual men participating in a study on HIV infection that was followed from seroconversion to AIDS. The patients were studied retrospectively for immunological functions of T cells, T-cell subset distribution and biological phenotype of HIV. A severe decrease in anti-CD3 monoclonal antibody (MAb)-induced T-cell proliferation at seroconversion was observed in two out of six men. After this acute phase, CD4+ T-cell numbers were in the normal range in the early asymptomatic period; the proliferative response was subnormal, whereas the capacity to generate cytotoxic T cells (CTL) was normal. From seroconversion on, CD4+CD29+ memory T-cell numbers were decreased to approximately 50% of normal values, which may contribute to loss of T-cell reactivity. In the asymptomatic phase only slow-replicating non-syncytium-inducing HIV variants were observed. The T-cell proliferative response further declined with the depletion of naive CD4+ CD45RA+ T cells and CD4+ T-cell numbers started to decline. This second decrease in T-cell function coincided with the emergence of more rapidly replicating, often (four out of six) syncytium-inducing variants. At diagnosis of AIDS, T-cell proliferation and CD4+ T-cell numbers were extremely low in five out of six patients and CTL function had declined in three out of five individuals tested. Circulating CD8+ cells had gradually shifted to an immature CD38+CD28- phenotype. Our findings support the theory that HIV-induced immune dysfunction allows for the emergence of virulent HIV variants associated with CD4+ cell loss and disease.
Gruters
R A
RA
Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Terpstra
F G
FG
De Goede
R E
RE
Mulder
J W
JW
De Wolf
F
F
Schellekens
P T
PT
Van Lier
R A
RA
Tersmette
M
M
Miedema
F
F
D000163:Acquired Immunodeficiency Syndrome / Q000453:epidemiology / Q000276:immunology* / Q000382:microbiology*; D000328:Adult; D015415:Biomarkers; D015331:Cohort Studies; D006679:HIV Seropositivity / Q000453:epidemiology / Q000276:immunology* / Q000382:microbiology*; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology; D006716:Homosexuality; D006801:Humans; D016130:Immunophenotyping; D008137:Longitudinal Studies; D008213:Lymphocyte Activation; D008297:Male; D016176:T-Lymphocyte Subsets / Q000276:immunology
D015415:Biomarkers