Thymus-derived cytokine(s) including interleukin-7 induce increase of T cell receptor alpha/beta+ 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) 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 suppressed by intraperitoneal injection of anti-interleukin-7 monoclonal antibody (mAb). The TcR alpha/beta T cells in FTEDC-implanted BALB/c nu/nu mice preferentially expressed V beta 11, although V beta 11-positive T cells are deleted in the thymus of euthymic BALB/c mice by clonal elimination of self-super-antigen Dvb11-specific T cells. TcR alpha/beta 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.
Kenai
H
H
Department of Immunology, Kyushu University, Fukuoka, Japan.
Matsuzaki
G
G
Nakamura
T
T
Yoshikai
Y
Y
Nomoto
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015704:CD4 Antigens / Q000032:analysis*; D016827:CD8 Antigens / Q000032:analysis*; D002454:Cell Differentiation; D016207:Cytokines / Q000502:physiology*; D005260:Female; D015851:Interleukin-7 / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D013950:Thymus Gland / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D015851:Interleukin-7; D016693:Receptors, Antigen, T-Cell, alpha-beta