Sun Yimin, Ge Bao-Sheng, Kasai Michiyuki, Diffendaffer Clara, Parks Nancy, Li Hanhan, Peng Jianxia, Langnas Alan N, Zhao Yong
Department of Surgery, University of Nebraska Medical Center, The Lied Transplant Center, Omaha, NE, USA.
Transpl Int. 2006 May;19(5):404-14. doi: 10.1111/j.1432-2277.2006.00300.x.
The ability of thymic epithelial cells (TEC) to re-educate mature T cells to be regulatory T cells has not been addressed. In the present study, this issue was directly investigated by co-culturing of mature T cells and allo-TECs. B6 macrophage cell line 1C21-cultured BALB/c splenocytes responded to B6 antigens in vitro. However, BALB/c splenocytes precultured with B6-derived TECs 1-4C18 or 1C6 did not proliferate to B6 antigens, but responded to rat antigens. Exogenous interleukin-2 (IL-2) failed to revise the unresponsiveness of these T cells. Allo-TEC-cultured T cells predominantly expressed Th2 cytokines (IL-4 and IL-10). B6 TEC-cultured BALB/c splenocytes markedly inhibited the immune responses of naïve BALB/c splenocytes to B6 antigens, but not to rat or the third-party mouse antigens. BALB/c nude mice that received naïve syngeneic splenocytes rejected B6 or rat skin grafts by 17 days postskin grafting; however, co-injection of B6 TEC-cultured BALB/c splenocytes significantly delayed B6 skin graft rejection (P < 0.01), with the unchanged rejection of rat skin grafts. These studies demonstrate that allo-TECs are able to 'educate' mature T cells to be regulatory cells, and suggest that regulatory cells derived from mature T cells by TECs may play an important role in T cell tolerance to allo- and auto-antigens.
胸腺上皮细胞（TEC）将成熟T细胞重新诱导为调节性T细胞的能力尚未得到研究。在本研究中，通过将成熟T细胞与同种异体TEC共培养直接研究了这个问题。用B6巨噬细胞系1C21培养的BALB/c脾细胞在体外对B6抗原产生反应。然而，用B6来源的TEC 1-4C18或1C6预培养的BALB/c脾细胞不会对B6抗原增殖，而是对大鼠抗原产生反应。外源性白细胞介素-2（IL-2）未能改变这些T细胞的无反应性。同种异体TEC培养的T细胞主要表达Th2细胞因子（IL-4和IL-10）。B6 TEC培养的BALB/c脾细胞显著抑制了未致敏的BALB/c脾细胞对B6抗原的免疫反应，但对大鼠或第三方小鼠抗原无抑制作用。接受未致敏同基因脾细胞的BALB/c裸鼠在皮肤移植后17天排斥B6或大鼠皮肤移植；然而，共同注射B6 TEC培养的BALB/c脾细胞显著延迟了B6皮肤移植的排斥反应（P<0.01），而大鼠皮肤移植的排斥反应未改变。这些研究表明，同种异体TEC能够将成熟T细胞“诱导”为调节性细胞，并表明TEC从成熟T细胞衍生的调节性细胞可能在T细胞对同种异体和自身抗原的耐受性中发挥重要作用。
