Number of CD4+ and CD8+ T-cell CDR3 clonotypes expanding during acute infection of macaques with simian immunodeficiency virus.

The total number of circulating CD4+ and CD8+ T-cells undergoing clonal expansions following SIV(mac251) infection was determined using a T-cell receptor Vbeta chain (TRBV) third complementarity-determining region (CDR3) DNA heteroduplex tracking assay (HTA). This assay measures the number of newly expanding T-cell clones but not their antigenic specificity. Fewer expanding CD4+ (3-23 per animal) than CD8+ (18-37 per animal) clonotypes were observed during the acute phase of SIV infection. CD8+ T-cell expansions peaked at 4 weeks postinfection (wpi) concomitant with early reductions in viremia. Expanding clone TRBV transcripts ranged in frequency from the limit of detection of 2% to 40% of their TRBV subfamily's transcripts. The number of expanding CD4+ or CD8+ clones correlated with neither peak, subsequent slope, nor steady-state viremia. CDR3 repertoires in CD8-expressing cells in different anatomical compartments were also analyzed. Repertoires were polyclonal in the thymus, oligoclonal in mesenteric lymph nodes, peripheral blood mononuclear cells (PBMC), and spleen, and extremely oligoclonal in intra-epithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL). The lack of correlation between the number of expanding T-cell clonotypes and viremia levels may reflect the highly variable selection pressure imposed on SIV by T-cell responses targeting different epitopes in outbred macaques.