Thymus‐derived cytokine(s) including interleukin‐7 induce increase of T cell receptor α/β⁺ CD4⁻CD8⁻ T cells which are extrathymically differentiated in athymic nude mice

Extrathymic T cell differentiation pathways have been reported, although the thymus is the main site of T cell differentiation. The thymus is also known to produce several cytokines that induce proliferation of thymocytes. In the present study, we investigated the influence of thymus‐derived cytokines on extrathymic T cell differentiation by intraperitoneal implantation with a diffusion chamber which encloses fetal thymus (we named it fetal thymus‐enclosed diffusion chamber, FTEDC) in athymic BALB/c nu/nu mice. Increase in number of T cells bearing T cell receptor (TcR) α/β 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 suppressed by intraperitoneal injection of anti‐interleukin‐7 monoclonal antibody (mAb). The TcR α/β T cells in FTEDC‐inplanted BALB/c nu/nu mice preferentially expressed Vβ11, although Vβ11‐positive T cells are deleted in the thymus of euthymic BALB/c mice by clonal elimination of self‐superantigen Dvb 11‐specific T cells. TcR α/β T cells in FTEDC‐implanted nude mice were of CD4⁻CD8⁻ phenotype and showed no proliferative response against anti‐TcR monoclonal antibody stimulation. These results suggest that the thymus can induce extrathymic T cell differentiation through the influence of thymus‐derived cytokine(s) including interleukin‐7, and that such extrathymically differentiated T cells have acquired only a little or no ability for proliferation when they recognize antigen by their TcR.