THYMUS-DERIVED CYTOKINE(S) INCLUDING INTERLEUKIN-7 INDUCE INCREASE OFT-CELL RECEPTOR-ALPHA BETA-CD8- T-CELLS WHICH ARE EXTRATHYMICALLY DIFFERENTIATED IN ATHYMIC NUDE-MICE( CD4)

Extrathymic T cell differentiation pathways have been reported, althou gh the thymus is the main site of T cell differentiation. The thymus i s also known to produce several cytokines that induce proliferation of thymocytes. In the present study, we investigated the influence of th ymus-derived cytokines on extrathymic T cell differentiation by intrap eritoneal implantation with a diffusion chamber which encloses fetal t hymus (we named it fetal thymus-enclosed diffusion chamber, FTEDC) in athymic BALB/c nu/nu mice. Increase in number of T cells bearing T cel l receptor (TcR) alpha/beta was detected in lymph nodes and spleens of FTEDC-implanted nude mice 1 week after implantation, whereas no such increase was detected in control nude mice implanted with a diffusion chamber without thymus. The FTEDC-induced increase of T cells was supp ressed by intraperitoneal injection of anti-interleukin-7 monoclonal a ntibody (mAb). The TcR alpha/beta T cells in FTEDC-inplanted BALB/c nu /nu mice preferentially expressed Vbeta11, although Vbeta11-positive T cells are deleted in the thymus of euthymic BALB/c mice by clonal eli mination of self-superantigen Dvb11-specific T cells. TcR alpha/beta T cells in FTEDC-implanted nude mice were of CD4-CD8- phenotype and sho wed no proliferative response against anti-TcR monoclonal antibody sti mulation. These results suggest that the thymus can induce extrathymic T cell differentiation through the influence of thymus-derived cytoki ne(s) including interleukin-7, and that such extrathymically different iated T cells have acquired only a little or no ability for proliferat ion when they recognize antigen by their TcR.