THE ROLE OF BALB C DONOR CD8(+) LYMPHOCYTES IN GRAFT-VERSUS-HOST DISEASE IN (BALB/CXA/J)F-1 (CAF1) MICE/

To investigate the role of donor T lymphocyte subsets in the developme nt of chronic graft-vs-host disease (GVHD) induced in (BALB/c x A/J)F- 1 (CAF1) mice by injecting BALB/c lymphoid cells, we analyzed the effe ct that CD8(+) cell removal from donor inoculum has on the manifestati on of the disease, Compared with age- and sex-matched CAF1 mice inject ed with whole lymphocyte inoculum, CAF1 mice injected with CD8(+)-depl eted inoculum exhibited: 1) a higher incidence and exacerbation of nep hritis by immunocomplexes; 2) higher (five- to sevenfold) spontaneous IL-4 production; 3) higher frequency titer and precocity of anti-dsDNA , anti-histone, and IgM and IgG rheumatoid factors; 4) a dramatic chan ge in the frequency and titer of anti-U1 small nuclear ribonucleoprote in Abs; and 5) a markedly decreased engraftment (10- to 15-fold) on BA LB/c donor lymphocytes. In contrast, rheumatoid arthritis-like disease , a later clinical manifestation of the GVHD in CAF1 + BALB/c model, i s not present in the CD8(+)-depleted model (CAF1 + CD8(-)BALB/c). Cons idered together, these data suggest that CD8(+) donor T lymphocytes pl ay an important role in the degree of chimerism, modulation of the res ponse to autoantigens, and clinical aspects developed in the GVHD mode l presented here.