An enlarged subpopulation of T lymphocytes bearing two distinct γδ TCR in an HIV-positive patient

Abstract

Although T cell clone monospecificity is ensured by several allelic exclusion processes operating at either the genotypic or phenotypic levels, clones expressing two distinct αβ or γδ TCR have been described in several instances. Thus far, the origin of dual TCR-expressing cells and the homeostatic mechanisms controlling the size of this subset in the periphery remain poorly understood. In the course of a phenotypic analysis of γδ T cells in HIV-infected patients, we detected the presence of a T cell subset stained by both V(δ)2- and V(δ)3-specific mAb, which represented a large fraction (up to 16.5%) of γδ peripheral blood lymphocytes (PBL) in one HIV patient. The presence of two distinct functional δ chains on these cells was confirmed by phenotypic and molecular analysis of TCR transcripts expressed by V(δ)2+V(δ)3+ T cell clones derived from this patient. For 18 months, the absolute number of these cells varied similarly to the other PBL subsets, before becoming undetectable in blood samples. Moreover, most of these cells expressed CD8 receptors, which are classically found on activated, but not resting, γδ T cells. Taken together, these data suggest that dual TCR-expressing T cells are subjected to peripheral expansions and contractions presumably following antigen recognition, which would argue against a systematic counter-selection of these cells during peripheral antigen-driven responses.