INDUCTION OF MURINE GAMMA-DELTA T-CELLS CYTOTOXIC FOR XENOGENEIC RAT-CELLS

C57BL/6 mice deprived or nondeprived of CD4(+) and CD8(+) T cells by m Abs were challenged with a rat T cell line, W7TM-1. Spleen cells obtai ned from CD4- and CD8-depleted animals rejecting W7TM-1 were examined by cytofluorometry, which demonstrated the presence of highly increase d gamma delta type CD4(-)CD8(-) T cell population (30 to 50% of entire T cells). In vitro sensitization of these spleen cells with W7TM-1 ge nerated a mixture of gamma delta and alpha beta type CD4(-)CD8(-) CTL for W7TM-1. Repeated stimulation of these cells with W7TM-1 resulted i n a gamma delta-type T cell population with more than 95% purity by da y 45. In contrast, alpha beta type CD8(+) CTL for W7TM-1 were induced from mice nondeprived of CD4(+) and CD8(+) T cells. Both gamma delta-t ype CD4(-)CD8(-) CTL and alpha beta type CD8(+) CTL were cytotoxic for rat cells in a species-specific manner. However, only reactivity of g amma delta type CD4(-)CD8(-) CTL, but not alpha beta type CTL, was inh ibited by a mAb for TCR-gamma delta. The gamma delta type CD4(-)CD8(-) CTL clones were also prepared from spleen cells derived from CD4- and CD8-depleted mice. They were also reactive for xenogeneic cells in a species-specific manner. Spleen cells derived from CD4- and CD8-deplet ed mice rejecting the whole-layer rat skin grafts were in vitro sensit ized with rat spleen cells, which also generated gamma delta type CD4( -)CD8(-) CTL specific for rat cells. V gamma 1 was detected as a major V gamma gene expressed in this gamma delta population by reverse tran scriptase-PCR. Cytotoxicity for xenogeneic cells may represent one of major function of gamma delta T cells.