Flexible migration program regulates γδ T-cell involvement in humoral immunity

gammadelta T cells are inadequately defined both in terms of their migration potential and contribution to antimicrobial immunity. Here, we have examined the migration profile of human blood gammadelta T cells and related cell lines and correlated these findings with their distribution in secondary lymphoid tissues and their function in B-cell cocultures. We find that resting gammadelta T cells are characterized by an inflammatory migration program similar to cells of the innate immune system. However, T-cell receptor (TCR) triggering resulted in the rapid but transient induction of a lymph node (LN)-homing program, as evidenced by functional CCR7 expression and concomitant reduction in expression and function of CCR5 and, to a lesser degree, CCR2. Moreover, the LN-homing program was reflected by the presence of gammadelta T cells in gastrointestinal lymphoid tissues, notably in clusters within germinal centers of B-cell follicles. In line with these findings, VgammaVdelta-TCR triggering re-suited in prominent expression of essential B-cell costimulatory molecules, including CD40L, OX40, CD70, and ICOS. Furthermore, gammadelta T cells were shown to provide potent B-cell help during in vitro antibody production. Collectively, our findings agree with a role for gammadelta T cells in humoral immunity during the early phase of antimicrobial responses. (C) 2003 by The American Society of Hematology.