High frequency of circulating γδ T cells with dominance of the V(δ)1 subset in a healthy population.

Abstract

TCR γδ+ cells constitute <5% of all circulating T cells in healthy, adult Caucasians, and Vδ1+ cells constitute a minority of these cells. In contrast to TCR αβ+ cells, their repertoire is selected extrathymically by environmental antigens. Although increased frequencies of Vδ1+ cells are found in several diseases, their function remains obscure. Here we show that the frequency of peripheral blood γδ T cells in healthy West Africans is about twice that of Caucasians, mainly due to a 5-fold increase in Vδ1+ cells, which is consequently the dominant subset. No age dependency of Vδ1 frequencies was identified and the Vδ1+ cells in the African donors did not show preferential Vγ chain usage. Analysis of the CDR3 region size did not reveal any particular skewing of the Vδ1 repertoire, although oligoclonality was more pronounced in adults compared to children. The proportions of CD8+, CD38+ and CD45RAhiCD45RO– cells within the Vδ1+ subset were higher in the African than in the European donors, without obvious differences in expression of activation markers. No significant correlations between levels of Vδ1+ cells and environmental antigens or immunological parameters were identified. Taken together, the evidence argues against a CDR3-restricted, antigen-driven expansion of Vδ1+ cells in the African study population. Our study shows that high frequencies of TCR γδ+ cells with dominance of the Vδ1+ subset can occur at the population level in healthy people, raising questions about the physiological role of Vδ1+ T cells in the function and regulation of the immune system.