Antiretroviral therapy restores diversity in the T-cell receptor Vbeta repertoire of CD4 T-cell subpopulations among human immunodeficiency virus type 1-infected children and adolescents.
Human immunodeficiency virus (HIV) type 1 infection perturbs the T-cell receptor (TCR) Vbeta repertoire. The TCR CDR3 length diversity of individual Vbeta families was examined within CD45RA and CD45RO CD4 T cells to assess the impact of the virus on clonality throughout CD4 T-cell activation and differentiation. A cross-sectional and longitudinal cohort study of 13 HIV-infected and 8 age-matched healthy children and adolescents examined the Vbeta CDR3 length profiles within CD4 T-cell subsets by the use of spectratyping. HIV-infected subjects demonstrated higher numbers of perturbations in CD4 CD45RA T cells (5.8 +/- 4.9 Vbeta families) than healthy individuals (1.6 +/- 1.8 Vbeta families) (P = 0.04). Surprisingly, CD4 CD45RO central memory T cells from infected subjects showed no increased perturbations compared to the perturbations for the same cells from healthy subjects (2.9 +/- 3.1 and 1.1 +/- 1.8 Vbeta families, respectively; P = 0.11). CD4 CD45RA TCR perturbations were higher among infected subjects with >25% CD4 cells than healthy subjects (mean number of perturbed Vbeta families, 6.6 +/- 5.4; P = 0.04). No correlations between perturbations in CD4 subsets and pretherapy age or viral load were evident. In contrast to CD8 T cells, HIV induces TCR disruptions within CD45RA but not CD45RO CD4 T cells. Therapy-induced viral suppression resulted in increases in thymic output and the normalization of the diversity of TCR within CD45RA CD4 T cells after 2 months of treatment. Perturbations occur prior to CD4 T-cell attrition and normalize with effective antiretroviral therapy. The impact of HIV on the diversity of TCR within naïve, central memory, and effector memory CD4 T cells is distinctly different from that in CD8 T cells.
Yin
Li
L
Department of Pathology, Immunology and Laboratory Medicine, Shands Cancer Center, University of Florida, College of Medicine, Gainesville, Florida, USA.
Kou
Zhong Chen
ZC
Rodriguez
Carina
C
Hou
Wei
W
Goodenow
Maureen M
MM
Sleasman
John W
JW
D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D055815:Young Adult
D019380:Anti-HIV Agents; D011948:Receptors, Antigen, T-Cell