Although their precise roles are not well defined, gammadelta T lymphocytes are recognized as regular components of immune responses. These cells express a limited T cell receptor repertoire and they can be stimulated by soluble ligands without conventional processing and presentation by major histocompatibility antigens. Progress in this area has been limited by the substantial differences between murine and human gammadelta T cells and the lack of knowledge about these cells in nonhuman primates. We used molecular analysis of T cell receptor diversity to characterize gammadelta T cell populations from peripheral blood and colon of rhesus macaques (Macaca mulatta). The gammadelta T cell receptor diversity was limited and distinct for these tissue compartments, particularly in the TCRGV2 family. Furthermore, the TCRDV1 + subset of peripheral blood gammadelta T cells showed signs of progressive oligoclonalization as a function of age. Similar observations have been reported for human tissue samples and our results validate rhesus macaques as an appropriate animal model for studying primate gammadelta T cell populations.

No abstract

γδ T cells show preferential homing that is characterized by biased TCR repertoire at different anatomical locations. The processes that regulate this compartmentalization are largely unknown. A model that allows repeated multiple sample procurement under different conditions and enables with relatively straightforward extrapolation to a human situation will facilitate our understanding. The peripheral blood Vγ2 T cell population is the best-characterized human γδ T cell subset. To determine its diversity at multiple immunocompartments matching blood, colon, and vagina samples from rhesus macaques were investigated. Four joining segments used in Vγ2-Jγ transcripts were identified, including one segment with no human counterpart. Like in humans, the rhesus peripheral blood Vγ2 TCR repertoire was limited and contained common sequences that were shared by genetically heterogeneous animals. Furthermore, this subset comprised several phylogenetically conserved Vγ2 complementarity-determining region 3 (CDR3) motifs between rhesus and humans. Common sequences were also found within the colon and vagina of the same animal, and within the peripheral blood and intestine of different unrelated animals. These results validate rhesus macaques as a useful model for γδ TCR repertoire and homing studies. Moreover, they provide evidence that the concept of limited but overlapping Vγ TCR repertoire between unrelated individuals can be extended including the mucosa of the digestive and reproductive tract.