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

Abstract

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.

Intestinal Specific Overexpression of Interleukin-7 Attenuates the Alternation of Intestinal Intraepithelial Lymphocytes After Total Parenteral Nutrition Administration

“…Similarly, other groups have reported that IL-7 knockout and IL-7R knockout mice show distinct declines in absolute numbers of thymocytes and IEL 23. Kanai et al 39 found that anti-IL-7 antibody treatment disturbed the induction of αβ-TCR+ T-cells after athymic nude mice were implanted with fetal thymocytes. In our present study, intestinal EC specific over-expression of IL-7 resulted in a significant increase in the total number of IEL, and significant changes in IEL phenotype and increases in the level of IEL proliferation.…”

Thymic and extrathymic origins of gut intraepithelial lymphocyte populations in mice.

“…The thymus could also act through the production of soluble factors, such as IL-7. It has been shown that implantation of a thymic stroma within a cell-impermeable chamber can increase some T cell populations in nude mice (22). Alternatively, immature precursors may reach not only the gut epithelium but also the thymus, in which they might expand, then migrate and complete their differentiation in the gut wall.…”

Progenies of fetal thymocytes are the major source of CD4−CD8+ αα intestinal intraepithelial lymphocytes early in ontogeny

“…Indeed, we have previously demonstrated that the IEL of nude and NTX mice have far larger numbers of CD3-IEL than their euthymic counterparts early in ontogeny [ll]. The concept that the thymus can influence differentiation or development of extrathymically derived T cells is not without merit [27,28]. Although some recent reports suggest that some CD3-IEL develop into CD3+ IEL extrathymically [29,30], this has not been definitely established.…”