Clonal Dominance Patterns of CD8 T Cells in Relation to Disease Progression in HIV-Infected Children

Abstract

CD8 T cells are important mediators of cellular immune responses as evidenced by clonal expansions in the CD8 TCR Vβ repertoire during primary HIV infection in adults. This study investigated the CD8 TCR Vβ repertoire by complementarity-determining region 3 length analysis using multiplex PCR in purified peripheral blood CD8 T cells of 22 HIV-infected children (age range was 0.75–15 yr, mean was 8.2 ± 4.1 yr). Evidence of clonal dominance in one or more Vβ families was obtained in 15 of 22 children. The patterns of clonal dominance were designated as major, minor, single, and none to indicate the involvement of three or more, two, one, or no Vβ families, respectively. A pattern of major or minor clonal dominance was observed in 12 children (group 1), whereas 10 children had single or no clonal dominance (group 2). In comparison with group 2, the children in group 1 had a higher percentage of CD4 cells (28.3 ± 11.6 vs 8.6 ± 4.8, p < 0.001); a higher stimulation index in lymphoproliferative responses to Candida (92.0 ± 59.5 vs 12.3 ± 14.4, p = 0.002), tetanus (76.3 ± 51.2 vs 11.2 ± 12.7, p = 0.002), and alloantigens (178.3 ± 298.9 vs 32.9 ± 35.2, p < 0.001); and a lower percentage of CD8+HLA-DR+CD38+ cells (37.4 ± 13.1 vs 54.6 ± 14.2, p < 0.01). The number of dominant CD8 T cell clones was significantly correlated with the percentage of CD4 T cells (r = 0.669, p < 0.001) but not with plasma HIV RNA. Compared with group 1, patients in group 2 had a 4.8 times greater probability of having <15% CD4 cells. These findings indicate that CD8 clonal dominance in HIV-infected children reflects robustness of immune responses, regardless of time since infection and virus load.