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

SUMMARY When MKL/lpr (H‐2 k ) spleen cells were intraperitoneally injected into C.B‐17‐scid/scid (severe combined immunodeficient (SCID)) (H‐2 d ) 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.