T cell repertoire expression in murine recipients of bone marrow transplant after LF 08-0299 (Tresperimus) administration

LF 08-0299 (Tresperimus), a novel immunosuppressive compound, has been prev iously shown to prevent graft-versus-host disease in murine models. In this study, we investigated the influence of LF 08-0299 on the TCR V beta reper toire of irradiated F1 recipient mice reconstituted with either syngeneic o r parental bone marrow cells. We showed that a partial blockade of thymic d ifferentiation occurred in normal mice under treatment at the transition CD 4(-)/CD8(-) to CD4(+)/CD8(+), and that this blockade was fully reversible. Despite the effect on the thymus, normal T cell repertoire negative selecti on was preserved following syngeneic bone marrow transplantation. We furthe r assessed whether LF 08-0299 administration could modify V beta T cell exp ression in irradiated recipients reconstituted with parental bone marrow ce lls. In our murine parental to F1 transplant model, abnormal TCR V beta 3, V beta 5, V beta 6 and V beta 11 expression was demonstrated in peripheral lymph nodes of irradiated recipients. Moreover, V beta 6 and V beta 3 T cel l populations were overexpressed. Administration of LF 08-0299 modified the pattern of V beta T cell expression. The expansion of V beta 6 T cells was selectively inhibited under LF 08-0299 therapy and, in contrast, V beta 5 T cells were overexpressed. Lymph node histological analysis showed that LF 08-0299 administration fully prevented the graft-versus-host reaction occu rring in untreated recipient mice.