Immunological and virological markers in individuals progressing from seroconversion to AIDS

Rob A. Gruters, Fokke G. Terpstra, Ruud E.Y. De Goede, Jan W. Mulder, Frank De Wolf, Peter T.A. Schellekens, René A.W. Van Lier, Matthijs Tersmette, Frank Miedeman*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

86 Citations (Scopus)

Abstract

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 acutephase, 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.

Original languageEnglish
Pages (from-to)837-844
Number of pages8
JournalAIDS
Volume5
Issue number7
DOIs
Publication statusPublished - Jul 1991
Externally publishedYes

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