The major subset of human peripheral blood γδ T cells expresses the Vγ2Vδ2 T cell receptor and responds to infectious diseases and malignancies. We observed a significant difference in the frequency of Vδ2 cells in blood from healthy Caucasian (CA) and African American (AA) age matched donors, with CA samples having 3.71%+4.37% Vδ2 cells (as a percentage of total lymphocytes) compared to 1.18%+2.14% Vδ2 cells for AA donors (p<0.0001). Levels of Granzyme B and CD56 expression on Vδ2 cells were lower for AA donors, and Vδ2 cells from AA donors displayed a less skewed Vδ2 chain repertoire (p<0.05). However, proliferative responses to phosphoantigens for AA donors and CA donors were similar. Thus, Vγ2Vδ2 cells in both groups were selected for phosphoantigen recognition, suggesting that differences in homeostatic regulation may account for an expanded population in CA individuals.
Differences in Vδ2 cell baseline frequencies across populations should be taken into account when studying diseases affecting the Vδ2 subset. A group of African-American HIV-infected patients who suppress HIV replication without antiretroviral therapy (natural viral suppressors, NVS) had a Vδ2 T cell frequency significantly lower than an age matched CA control group (1.28%+1.21% versus 3.71%+4.37%), but showed no decrease in the proportion of circulating Vδ2 T cells when compared with a control group appropriately matched for age and ethnicity (1.28+1.21 versus 1.18%+2.14%). In contrast, a group of AA HIV+ viremic patients had significantly lower values of circulating Vδ2 T cells than the same age and ethnicity matched control group (0.34 ±0.37% versus 1.18%+2.14%). Using appropriately matched controls revealed a significant association between natural viral suppression and normal levels of Vδ2 lymphocytes.