ANTIGEN-PRESENTING CELLS FOR NAIVE TRANSGENIC GAMMA-DELTA T-CELLS - POTENT ACTIVATION BY ACTIVATED ALPHA-BETA T-CELLS

The function of gamma delta T cells, particularly the minor population of circulating gamma delta T cells, remains unclear. To study these l ymphoid gamma delta T cells, a transgenic SCID mouse containing the KN 6 gamma delta TCR whose ligand is the TL gene product, T22(b), was cre ated. KN6-SCID mice contain a monoclonal population of naive KN6(+) ga mma delta T cells. Using these mice, we have studied the APC required for activation of KN6(+) gamma delta T cells in vitro and in vivo. Ana lysis of an in vitro mixed lymphocyte response identified a hierarchy of potency for stimulation: dendritic cells = T cell blasts > B cell b lasts > B cells > resting T cells. In contrast, in vivo, only cup T ce lls fully activated KN6(+) gamma delta T cells as measured by an incre ase in the number of splenic KN6(+) cells, the development of blast mo rphology, and the development of proliferative anergy in the respondin g KN6(+) cells. The strong stimulatory properties of C57BL/6J T cells appeared to depend on their having been activated by KN6-SCID alloanti gens. T cells from (C57BL/6J x BALB/c)F-1 mice, which are tolerant of KN6-SCID alloantigens, could not fully activate KN6(+) cells. However, the F-1 T cells could activate KN6(+) cells if they were activated in vivo by the mitogen, staphylococcal enterotoxin B, A mixture of third party activated T cells plus T22(b+) non-T cells only partially activ ated KN6(+) cells, implying that activated T22(b+) T cells are acting directly as stimulatory cells. Although the Ags recognized by gamma de lta T cells are generally unknown, Ag presentation by activated ap T c ells may be an important method of activation.