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

• Published in: Transplant immunology 1998-12, Vol.6 (4), p.217-224
• Main Authors: Annat, Jocelyne, Dutartre, Patrick
• Format: Article
• Language: English
• Subjects: Animals; Bone Marrow Transplantation - immunology; Carbamates - administration & dosage; Carbamates - pharmacology; Cell Differentiation - drug effects; Graft vs Host Disease - pathology; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - pharmacology; Lymph Nodes - cytology; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Receptors, Antigen, T-Cell, alpha-beta - biosynthesis; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Thymus Gland - cytology; Time Factors
• ISSN: 0966-3274; 1878-5492
• DOI: 10.1016/S0966-3274(98)80011-7

LF 08-0299 (Tresperimus), a novel immunosuppressive compound, has been previously shown to prevent graft-versus-host disease in murine models. In this study, we investigated the influence of LF 08-0299 on the TCR Vß repertoire of irradiated F1 recipient mice reconstituted with either syngeneic or parental bone marrow cells. We showed that a partial blockade of thymic differentiation occurred in normal mice under treatment at the transition CD4 −/CD8 − to CD4 +/CD8 +, and that this blockade was fully reversible. Despite the effect on the thymus, normal T cell repertoire negative selection was preserved following syngeneic bone marrow transplantation. We further assessed whether LF 08-0299 administration could modify Vß T cell expression in irradiated recipients reconstituted with parental bone marrow cells. In our murine parental to F1 transplant model, abnormal TCR Vß3, Vß5, Vß6 and Vß11 expression was demonstrated in peripheral lymph nodes of irradiated recipients. Moreover, Vß6 and Vß3 T cell populations were overexpressed. Administration of LF 08-0299 modified the pattern of Vß T cell expression. The expansion of Vß6 T cells was selectively inhibited under LF 08-0299 therapy and, in contrast, Vß5 T cells were overexpressed. Lymph node histological analysis showed that LF 08-0299 administration fully prevented the graft-versus-host reaction occurring in untreated recipient mice.