SummaryChanges in T cell receptor (TCR) V/3 repertoire and their correlation with virologic events were investigated in rhesus monkeys after acute infection with the simian immunodeficiency virus (SIV). 11 genetically defined rhesus monkeys were experimentally infected with SIVm~ or a chimeric simian-human immunodeficiency virus (SHIV), and their peripheral blood lymphocytes (PBL) and lymph nodes were prospectively assessed for TCR V~ gene expression. PBL and lymph nodes of the acutely infected monkeys demonstrated an expansion of selected V~-expressing T lymphocyte subpopulations as early as 3 d after infection. These expanded V/~-expressing lymphocyte subpopulations were comprised predominantly of CD8+ cells. Six of seven infected monkeys sharing a single electrophoreticaUy defined major histocompatibility complex class I allele exhibited a similar expansion of VB14-expressing PBL. Sequence analyses of V-D-J segments of TCR-fl cDNA indicated that the VB-expressing T cell subpopulation expansion can be oligoclonal. SIVm,c-specific CDS+ cytotoxic T lymphocytes were demonstrated in both PBL and lymph nodes of the infected monkeys at the time expansion of the selected V3-expressing cell subpopulations was seen. Finally, the expansion of the selected V3-expressing lymphocytes in PBL coincided with the emergence and clearance of SIV p27 from the plasma of the infected monkeys. These results demonstrate that acute infection of rhesus monkeys with SIVm~ or SHIV results in an expansion of CD8 + lymphocyte subpopulations expressing selected V3 gene families. The selectively expanded T lymphocytes may contribute to early viral clearance after acute SIVmac or SHIV infection.

The T-cell receptor (TCR) CDR3 length heterogeneity is formed during recombination of individual V␤ gene families. We hypothesized that CDR3 length diversity could be used to assess the fundamental differences within the TCR repertoire of CD45RA and CD45RO T-cell subpopulations. By using PCR-based spectratyping, nested primers for all 24 human V␤ families were developed to amplify CDR3 lengths in immunomagnetically selected CD45RA and CD45RO subsets within both CD4؉ and CD8 ؉ T-cell populations. Umbilical cord blood mononuclear cells or peripheral blood mononuclear cells obtained from healthy newborns, infants, and children, as well as human immunodeficiency virus (HIV)-infected children, were analyzed. All T-cell subsets from newborn and healthy children demonstrated a Gaussian distribution of CDR3 lengths in separated T-cell subsets. In contrast, HIV-infected children had a high proportion of predominant CDR3 lengths within both CD45RA and CD45RO T-cell subpopulations, most commonly in CD8 ؉ CD45RO T cells. Sharp differences in clonal dominance and size distributions were observed when cells were separated into CD45RA or CD45RO subpopulations. These differences were not apparent in unfractionated CD4؉ or CD8 ؉ T cells from HIV-infected subjects. Sequence analysis of predominant CDR3 lengths revealed oligoclonal expansion within individual V␤ families. Analysis of the CDR3 length diversity within CD45RA and CD45RO T cells provides a more accurate measure of disturbances in the TCR repertoire than analysis of unfractionated CD4 and CD8 T cells.

Human immunodeficiency virus (HIV) type 1 disrupts the T cell receptor (TCR) variable region (V) beta repertoire in CD8 T cells by impairing thymic capacity and skewing postthymic cellular maturation. The TCR repertoire was examined using spectratyping of CDR3 length diversity within CD45RA and CD45RO CD8 T cells in HIV-infected and healthy children. In healthy children, CDR3 lengths displayed Gaussian distribution in both CD45RA and CD45RO subsets. Vbeta families in HIV-infected children displayed a large proportion of perturbations in both subsets. High virus load and advanced immunosuppression correlated with increased perturbations within CD45RA but not CD45RO CD8 T cells. After therapy and virus suppression, there was rapid reestablishment of Gaussian distributions in CD45RA cells. HIV-1-induced disruption of TCR diversity within CD45RA CD8 T cells correlates with disease progression. Suppression of viral replication by treatment results in the rapid correction of TCR diversity in this CD8 subset because of emergence of new T cells from the thymus.