CD4-8- T-CELLS INCREASE IN MRL LPR MICE TREATED WITH THYMIC FACTORS/

The in vivo effect of thymic factors on immature lymphocytes was analy sed in MRL/lpr mice. This strain carries a genetic defect that causes during their life cycle a block of T-cell differentiation and abnormal proliferation of CD4(-)8(-) (double-negative, DN) T-lymphocytes. In v ivo administration of four preparations of thymic factors, thymopentin (TP-1), thymopoietin (TP-5), thymolymphotropin (TLT), and thymomoduli n (TMD) into young (2-month-old) MRL/lpr mice induced a significant in crease of DN T-cells both in the thymus and in the peripheral lymph no des, with a concomitant decrease of double-positive (DP) T-cells in th e thymus and of single-positive (SP) T-cells in the lymph nodes. The l evel of DNA fragmentation measured as propidium iodide fluorescence wa s increased in the thymus population of young mice and in the lymph no de population of old mice treated with TLT. SCID mice transplanted wit h lymph node cells from MRL/lpr donors (MRL-->SCID) developed graft ve rsus host (GVH) reaction due to the activation of MRL CD8(+) alloreact ive T-cells. This model was used to analyse the effect of TMD/TLT in v ivo on MRL cell proliferation and expansion; in fact, spleen cells fro m MRL-->SCID mice after treatment with TMD/TLT showed an increased cel l proliferation, and an expansion of DN T-cells with a concomitant dec rease of SP cells (both CD4(+) and CD8(+) cells). Decreased SP cell nu mbers in this context could explain why TMD/TLT treatment of SCID mice engrafted with MRL cells increased their survival compared to untreat ed MRL-->SCID mice.