Attenuation of lpr-graft-versus-host disease (GVHD) in MRL./lpr spleen cell-injected SCID mice by in vivo treatment with anti-Vβ8.1,2 monoclonal antibody

Abstract

SUMMARY When MKL/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 Ipr-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 (Vβ6, Vβ8.1,2 and Vβ11) revealed that the Vβ8.1,2+ 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-Vβ8.1,2+ (KJ16) MoAb, Vβ8.1,2+ T cells were markedly depleted, and the severity of/pr-GVHD was attenuated at 4 and 8 weeks after treatment, in contrast to normal rat IgG-injected SCID+MRL/lpr mice. However, the KJI6 MoAb-treated SCID-MRL/lpr mice suffered from severe lpr-GVHD 12 weeks after treatment, although Vβ8.1,2+ T cells were still maintained at a low level. These findings suggest that Vβ8.1,2+ T cells are a major T cell population (hat 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 Vβ8.1,2+ T cells, and contribute to the development of lpr-GVHD.