Major expansion of CD8+ T cells with a predominant Vβ usage during the primary immune response to HIV

Abstract

A SIGNIFICANT proportion (up to 70%) of individuals experience an acute clinical syndrome of varying severity associated with primary infection with the human immunodeficiency virus (HIV). We report here studies on six individuals who showed an acute HIV syndrome which generally resolved within four weeks, concomitant with a dramatic downregulation of viraemia. To characterize the T-cell-mediated primary immune response to HIV, we used combined semiquantitative polymerase chain reaction assay and cytofluorometry to analyse the T-cell antigen receptor repertoire in sequential peripheral blood mononuclear cells from the patients. We found major oligoclonal expansions in a restricted set of variable-domain beta-chain (V beta) families. Cells expressing the expanded V beta s predominantly expressed the CD8 T-cell differentiation antigen and mediated HIV-specific cytotoxicity. Major oligoclonal expansions of these CD8+ T lymphocytes may represent an important component of the primary immune response to viral infections and may help to clarify both the immunopathogenic and the protective mechanisms of HIV infection.

A Large Number of T Lymphocytes Recognize Moloney-Murine Leukemia Virus-Induced Antigens, but a Few Mediate Long-Lasting Tumor Immunosurveillance

“…However, despite alternative V␤ T cell priming, the immune response to M-MuLV-induced Ags is dominated by the almost exclusive expansion of T cell clones sharing V␤5 gene segments (17). These findings confirm the observations that the massive CD8 ϩ T cell expansion during viral infection (1, 2) in many cases is accompanied by the selection of a V␤ restricted T cell repertoire (7)(8)(9)(10)(11).…”

“…Furthermore, T cell responses often appear limited to a single encoded immunodominant peptide which generally stimulates a large number of specific CTL, while subdominant epitopes elicit T cell response that do not offer a high protection level against pathogens (5,6). Clonotypic analysis of CD8 T cell response in many cases provides evidence that immunodominant determinants are recognized by a restricted T cell repertoire that uses a limited number of TCRV␤ and/or V␣ domains (7)(8)(9)(10)(11).…”

Apoptosis of HIV-specific CD8+ T cells: an HIV evasion strategy

“…8 A vigorous oligoclonal CD8 þ T-cell response develops at a very early stage after acute infection. 9,10 This response reaches a peak at the same time when primary viremia starts to fall. 6,11 Following viral load decline, CD8 þ T cells are rapidly removed, presumably by apoptosis, while an HIV-specific CD8 þ T-cell population approximately 1% of total CD8 þ T cells finally remains in circulation.…”

Longitudinal analysis of B cell repertoire and antibody gene rearrangements during early HIV infection

“…T-cell repertoire perturbations were observed by others and us very early in the natural history of HIV infection. 13,14 Although the clinical consequences of these expansions and deletions of clonotypes remain uncertain, a clonally restricted T-cell antiviral repertoire and activity may impair the ability to recognize a broader range of HIV epitopes and emerging mutant species of the virus. Hence, a main objective of HIV therapy should be to rapidly restore and maintain a diverse T-cell population that will respond promptly to multiple viral epitopes.…”