CDR3-independent gamma delta V delta 1+ T cell expansion in the peripheral blood of HIV-infected persons.

A majority of circulating gamma delta T cells in humans express the V delta 2 variable segment associated with the V gamma 9 segment. A minor subset uses the V delta 1 gene mainly paired with a V gamma-chain from group I. Although little is known about the function and the Ags recognized by V delta 1 T cells, their expansion has been described in several diseases. Significant alterations of gamma delta subset distribution have been observed in PBMC from HIV-infected persons. In addition to their significant increase, gamma delta T cells showed an alteration in their subset representation because most of them expressed the V delta 1 receptor and, concomitantly, the V delta 2+ subset was under-represented. To gain insight into the mechanisms involved in this selective expansion, we characterized the V delta 1-J delta 1 junctional diversity in PBMC from healthy donors and HIV-infected individuals at different stages of the disease. We confirmed that the V delta 1 repertoire is restricted in most of the healthy donors. In HIV-infected subjects, we found that the increase of V delta 1 T cells is independent to a particular V gamma-chain expression, and the characterization of the TCR-delta diversity demonstrated a similar restricted V delta 1-J delta 1 rearrangement pattern, not significantly different from the pattern of healthy donors. Moreover, no amino acid junctional motif could be identified either in control or in HIV-infected donors. This report demonstrates that the V delta 1 selective expansion in the course of HIV infection is not the consequence of the emergence of some specifically CDR3-dependent expanded V delta 1 T cell clones. Interestingly, this subset showed an increased ability to be expanded in vitro in the presence of IL-2 alone and, although they did not harbor ex-vivo the phenotype of fully activated cells, they did express the activation marker CD38, a marker for disease progression. Altogether this report indicates that, although the patients' V delta 1 T cells seem to be in a pre-activated state, their selective expansion in the course of HIV infection is not the consequence of a peripheral CDR3-dependent antigenic selection.