Extrathymic Development of Self-Reactive γδ T Cells in Athymic BALB/cnu/nuMice

In the present report, we demonstrated that extrathymic γδ T cells proliferated in the mixed culture of lymph node cells of BALB/cnu/numice and irradiated syngeneic spleen cells (syngeneic MLR). Reverse transcription–polymerase chain reaction (RT-PCR) analyses revealed that Vδ5 and Vδ6 were dominantly expressed by the γδ T cells from the syngeneic MLR. Furthermore, the syngeneic MLR may expand Vδ5+T cells with BALB invariant delta (BID) sequence which is specifically detected in BALB background mice because Vδ5 RT-PCR products from syngeneic MLR were digested with anAluI restriction enzyme which cut the Dδ2–Jδ1 junction of the BID sequence but not those of most non-BID Vδ5 sequences. Interestingly, anti-mycobacterial and mammalian heat shock protein (Hsp) 60 mAb ML30 suppressed the generation of Vδ5 with anAluI site in syngeneic MLR. These results suggest that extrathymically derived Vδ5+and Vδ6+γδ T cells recognize BALB/c self antigens and that the Hsp60 or an Hsp60-related molecule may be involved in the anti-self response of Vδ5+BID+γδ T cells.