Visualization, fate, and pathogenicity of antigen-specific CD8(+) T cells in the graft-versus-host reaction

To follow the fate of alloreactive T cell effecters in graft-vs-host diseas e, L-d-specific CD8(+) T cells from C57BL/6 2C TCR-transgenic donors were t ransplanted into sublethally irradiated (750 cGy) Ld+ or Ld- recipients. In Ld- C57BL/6 or (BALB/c-dm2 x C57BL/6)F-1 recipients, naive 2C T cells engr afted and survived long term, but did not acquire effector function. In Ld (BALB/c x C57BL/6)F-1 recipients, 2C T cells engrafted, expanded, became c ytolytic, destroyed host B cells and double-positive thymocytes, and later disappeared. Despite marked damage to lymphoid and hemopoietic cells by 2C T cells, no significant pathology was detected in other organs, and recipie nts survived, Ld+ (BALB/c x C57BL/6)F-1 recipients died when LPS/endotoxin was administered on day 7 after cell transfer, while Ld- (BALB/c-dm2 x C57B L/6)F-1 recipients survived. Our findings show that under certain condition s, a CD8(+) T cell population recognizing an extremely limited repertoire o f Ags can initiate graft-vs-host disease.