HIV-INFECTION LEADS TO DIFFERENTIAL EXPRESSION OF T-CELL RECEPTOR V-BETA GENES IN CD4+ AND CD8+ T-CELLS

Objective: To analyse variation in T-cell receptor (TCR) Vbeta gene expression in T cells in HIV-infected individuals. Design: Because there are very few monoclonal antibodies available for studying TCR Vbeta gene expression, we used polymerase chain reaction (PCR) to analyse the TCR Vbeta repertoire in HIV-infected individuals using specific primers for 20 distinct families of TCR Vbeta. Methods: Evaluation of TCR Vbeta gene expression in peripheral blood from HIV-1-infected individuals [two in Centers for Disease Control (CDC) stage II, five in CDC stage III and four in CDC stage IV]. Complementary DNA was produced from CD4+ and CD8+ T cells, amplified by PCR and analysed after Southern blotting and hybridization with a Cbeta-specific oligonucleotide probe. Results: Vbeta gene expression was dramatically modified, especially in AIDS patients. The CD4+ T-cell subset showed both overexpression (Vbeta2) and deletions or underexpression (Vbeta9-Vbeta20), whereas these gene segments were expressed normally in the CD8+ subset. Only Vbeta 3 was deleted or underexpression in both CD4+ and CD8+ populations in AIDS patients. Conclusions: HIV-1 infection induces CD4+ T-cell deficiency, both in total numbers and by causing a paucity of select Vbeta gene expression in this subset. In addition, the Vbeta3 gene family was deleted or underexpressed was observed in both CD4+ and CD8+ T-cell subsets from patients in CDC stage IV. These results are compatible with changes in Vbeta gene expression known to occur under the action of endogenous or exogenous superantigens.