Defect in negative selection in 1pr donor-derived T cells differentiating in non-lpr host thymus

Abstract

Transplantation of bone marrow cells of lpr/lpr mice into irradiated normal mice fails to develop massive lymphadenopathy or autoimmunity but causes severe graft-vs.-host-like syndrome. To elucidate an abnormality of lpr/lpr bone marrow-derived T cells, we transplanted bone marrow cells of Mlsb lpr/lpr mice into H-2-compatible Mlsa non-lpr mice. Although lpr/lpr T cell precursors repopulated the host thymus as well as +/+ cells, a proportion of CD4+ CD8+ cells decreased, and that of both CD4- and CD8- single-positive cells increased compared with those of +/+ recipients. Notably, in MRL/lpr · AKR and C3H/lpr · AKR chimeras, CD4 single-positive thymocytes contained an increased number of Vβ6+ cells in spite of potentially deleting alleles of Misa, whereas Vβ6+ mature T cells were deleted in the MRL/+ → AKR and C3H/+ → AKR chimeras. There was no difference between MRL/+ → AKR and MRL/lpr → AKR chimeras in their proportion of Vβ3+ cells because both host and donor strain lack the deleting alleles. Interleukin 2 receptor expression of mature T cells, in the thymus and lymph node, was obviously higher in the MRL/lpr → AKR chimeras, in particular in the ̈forbidden̈ Vβ6+ subset. Moreover, lpr donor-derived peripheral T cells showed vigorous anti-CD3 response. These results indicate that lpr-derived T cells escape not only tolerance-related clonal deletion but also some induction of unresponsiveness in the non-lpr thymus.