Attenuation of lpr-graft-versus-host disease (GVHD) in MRL/lpr spleen cell-injected SCID mice by in vivo treatment with anti-V beta 8.1,2 monoclonal antibody.

When MRL/lpr (H-2k) spleen cells were intraperitoneally injected into C.B-17-scid/scid (severe combined immunodeficient (SCID)) (H-2d) mice, the SCID (SCID-MRL/lpr) mice manifested a severe wasting syndrome with weight loss, splenic atrophy, and lymphoid cell infiltration in the liver and lung, as seen in lpr-GVHD. In contrast, MRL/+ spleen cell-injected SCID (SCID-MRL/+) mice did not show lpr-GVHD. The spleens of SCID-MRL/lpr mice showed progressive increases in donor CD4+ and CD8+ T cells from 4 to 12 weeks after injection and a decrease in B cells at 12 weeks. SCID-MRL/+ mice showed a stable engraftment of CD4+ and CD8+ T cells and a progressive increase in B cells. Analyses of T cell receptor (TCR) repertoires (V beta 6, V beta 8.1,2 and V beta 11) revealed that the V beta 8.1,2+ T cells were found more frequently in SCID-MRL/lpr mice than in SCID-MRL/+ mice. When SCID-MRL/lpr mice were treated with intraperitoneal injection of an anti-V beta 8.1,2 (KJ16) MoAb, V beta 8.1,2+ T cells were markedly depleted, and the severity of lpr-GVHD was attenuated at 4 and 8 weeks after treatment, in contrast to normal rat IgG-injected SCID-MRL/lpr mice. However, the KJ16 MoAb-treated SCID-MRL/lpr mice suffered from severe lpr-GVHD 12 weeks after treatment, although V beta 8.1,2+ T cells were still maintained at a low level. These findings suggest that V beta 8.1,2+ T cells are a major T cell population that mediates lpr-GVHD in the early stage of lpr-GVHD, but that in the later stage, the other T cell populations may proliferate naturally or in accordance with the depletion of V beta 8.1,2+ T cells, and contribute to the development of lpr-GVHD.