Population level effects on Vγ2Vδ2 T cell frequencies in healthy adults: a difference in baseline values and resting phenotypes among Caucasian and African American donors (132.16)

Abstract

Abstract Adult human γδ T cells are dominated by the Vγ2Vδ2 T cell receptor (TCR) which modulates MHC-unrestricted responses to non-peptidic antigens. This subset is so numerous that between 1 in 40 and 1 in 400 circulating CD3+ T cells will respond to stimulation with isoprenoid pyrophosphates. The normal frequency of Vγ2Vδ2+ cells reflects TCR selection and amplification by chronic antigen stimulation, but the regulatory mechanisms controlling population size have not been described. During clinical studies related to Vγ2Vδ2 T cells in cancer and AIDS, we identified a difference in the circulating populations between Caucasian and African American healthy volunteers. When expressed as the percentage of total lymphocytes, Caucasian donors had 5-times higher levels of Vγ2Vδ2 cells compared to African American donors and phenotypes characteristic of mature functional cells were also different among the groups, including CD56 expression that is linked to cytotoxicity. Analysis of the Vg2 repertoire showed a strikingly lower proportion of cells expressing the Vγ2-Jγ1.2 rearrangement. Our data suggest that distinct regulatory mechanisms, in addition to positive selection and chronic amplification, control Vγ2Vδ2 cell levels in blood and that further study of population level effects may uncover unique regulatory mechanisms that control this interesting population.