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 mino r subset uses the V delta 1 gene mainly paired with a V gamma-chain fr om group I. Although little is known about the function and the Ags re cognized by V delta 1 T cells, their expansion has been described in s everal diseases. Significant alterations of gamma delta subset distrib ution have been observed in PBMC from HIV-infected persons. In additio n to their significant increase, gamma delta T cells showed an alterat ion in their subset representation because most of them expressed the V delta 1 receptor and, concomitantly, the V delta 2(+) subset was und er-represented. To gain insight into the mechanisms involved in this s elective expansion, we characterized the V delta 1-J delta 1 junctiona l diversity in PBMC from healthy donors and HIV-infected individuals a t different stages of the disease. We confirmed that the V delta 1 rep ertoire is restricted in most of the healthy donors. In HIV-infected s ubjects, we found that the increase of V delta 1 T cells is independen t to a particular V gamma-chain expression, and the characterization o f 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 co uld be identified either in control or in HIV-infected donors. This re port demonstrates that the V delta 1 selective expansion in the course of HIV infection is not the consequence of the emergence of some spec ifically CDR3-dependent expanded V delta 1 T cell clones. Interestingl y, 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 t he 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 i n a pre-activated state, their selective expansion in the course of HI V infection is not the consequence of a peripheral CDR3-dependent anti genic selection.