Mouse Sertoli cells display phenotypical and functional traits of antigen-presenting cells in response to interferon gamma
Mouse Sertoli cells display phenotypical and functional traits of antigen-presenting cells in response to interferon gamma
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DOI：
10.1095/biolreprod.107.063578
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发表时间：
2008-02-01
影响因子：
3.6
通讯作者：
Filippini, Antonio
中科院分区：
文献类型：
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作者：
Dal Secco, Valentina;Riccioli, Anna;Filippini, Antonio
睾丸被认为是免疫特权部位，因为它可以耐受自身抗原生殖细胞或同种异体移植物。由于血睾屏障是一个不完整的免疫屏障，我们探讨了是否支持细胞，生精上皮的体细胞，可能发挥积极的作用，在免疫逃避。我们报告的数据表明，B7-H1（正式称为CD 274）介导的共抑制，细胞间相互作用的基础上的免疫调节机制，可以激活支持细胞淋巴细胞共培养。我们已经发现，在干扰素γ（IFNG）的反应中，小鼠支持细胞强烈上调负共刺激配体B7-H1，但仍然缺乏正共刺激分子。阻断Sertoli细胞表面的B7-H1导致与Sertoli细胞共培养的CD 8（+）T细胞增殖增强。此外，IFNG刺激的支持细胞被发现表达，同时与B7-H1，MHC II类。因此，我们假设支持细胞可以作为非专职致耐受性抗原呈递细胞诱导富集在调节性T细胞（T细胞）的混合T淋巴细胞群体。有趣的是，我们发现T细胞与Sertoli细胞共培养确实可以诱导CD 4（+）CD 25（+）（正式称为IL 2 RA）FOXP 3（+）T细胞的增加和CD 4（+）CD 25（-）T细胞的减少，表明Sertoli细胞介导的Treg转化;发现该过程是B7-H1非依赖性的。总之，这些数据表明，支持细胞可能能够下调局部免疫应答，一方面通过B7-H1直接抑制CD 8 + T细胞增殖，另一方面通过诱导可能抑制其他旁观者T细胞的TcR增加。
The testis is regarded as an immunologically privileged site because it tolerates either autoantigenic germ cells or allografts. Because the blood testis barrier represents an incomplete immunological barrier, we have explored whether Sertoli cells, the somatic cells of the seminiferous epithelium, might play an active role in immune evasion. We report data indicating that B7-H1 (officially known as CD274)-mediated co-inhibition, an immunomodulatory mechanism based on cell-cell interaction, can be activated in Sertoli cell-lymphocyte cocultures. We have found that, in response to interferon gamma (IFNG), mouse Sertoli cells strongly up-regulate the negative co-stimulatory ligand B7-H1 but remain devoid of positive co-stimulatory molecules. Blockade of B7-H1 on the Sertoli cell surface resulted in enhanced proliferation of CD8(+) T cells cocultured with Sertoli cells. Moreover, IFNG-stimulated Sertoli cells were found to express, concurrent with B7-H1, MHC class II. Therefore, we have hypothesized that Sertoli cells could function as nonprofessional tolerogenic antigen-presenting cells by inducing enrichment in regulatory T cells (Tregs) in a mixed T lymphocyte population. Interestingly, we found that coculturing T cells with Sertoli cells can indeed induce an increase in CD4(+)CD25(+)(officially known as IL2RA)FOXP3(+) Tregs and a decrease in CD4(+)CD25(-) T cells, suggesting Sertoli cell-mediated Treg conversion; this process was found to be B7-H1-independent. Altogether these data show that Sertoli cells are potentially capable of down-regulating the local immune response, on one hand by directly inhibiting CD8+ T cell proliferation through B7-H1 and, on the other hand, by inducing an increase in Tregs that might suppress other bystander T cells.