Induction of eye-derived tolerance does not depend on naturally occurring CD4+CD25+ T regulatory cells
Induction of eye-derived tolerance does not depend on naturally occurring CD4+CD25+ T regulatory cells
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DOI：
10.1167/iovs.05-0110
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发表时间：
2006-03-01
影响因子：
4.4
通讯作者：
Stein-Streilein, J
中科院分区：
文献类型：
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作者：
Keino, H;Takeuchi, M;Stein-Streilein, J
目的.调节性CD 4（+）T细胞（T细胞）出现在患有前房相关免疫偏离（ACAID）的小鼠的脾脏中，ACAID是通过将抗原注射到眼前房（AC）中诱发的眼源性耐受。本研究旨在探讨这些T细胞是否表达CD 25，是否来源于天然的CD 4（+）CD 25（+）T细胞。来自D 011的初始T细胞。10只小鼠在体外用卵清蛋白（OVA）脉冲的、TGF β处理的抗原呈递细胞（APC）激活，并通过流式细胞术测定CD 25的表达。从DO 11的脾脏获得OVA特异性ACAID T细胞。10只患有ACAID至OVA的小鼠。在将CD 4（+）CD 25（+）和CD 4（+）CD 25（-）ACAID T细胞注射入OVA免疫小鼠或检测调节性T细胞转录因子Foxp 3的mRNA表达之前，使用免疫磁性富集来分选CD 4（+）CD 25（+）和CD 4（+）CD 25（-）ACAID T细胞。此外，在AC注射OVA之前，通过向小鼠中注射抗IL-2受体抗体来进行CD 25（+）T细胞的全身耗竭。来自DO 11的OVA特异性T细胞。10只小鼠在暴露于OVA脉冲的、TGF β处理的APC时表达CD 25，即使当D011.10 T细胞在其体外刺激之前耗尽CD 25+细胞时也是如此。此外，在注射CD 4 + CD 25+或CD 4（+）CD 25（-）ACAID T细胞的幼稚小鼠中，DH受到抑制。CD 44（+）CD 25（+），而CD 4（+）CD 25（-），ACAID T细胞表达Foxp 3。最后，在去除CD 25（+）细胞的小鼠中，OVA诱导ACAID。ACAID的一些CD 4（+）T细胞来源于CD 25（-）前体，并且ACAID的诱导不依赖于天然CD 4（+）CD 25（+）T细胞的存在。
PURPOSE. Regulatory CD4(+) T cells (T regs) arise in the spleens of mice with anterior chamber-associated immune deviation (ACAID), an eye-derived tolerance evoked by injection of antigen into the ocular anterior chamber (AC). The current study was conducted to investigate the possibility that these T regs express CD25 and are derived from natural CD4(+)CD25(+) T cells.METHODS. Naive T cells from DO11. 10 mice were activated in vitro by ovalbumin (OVA)-pulsed, TGF beta-treated antigen-presenting cells (APCs), and the expression of CD25 assayed by flow cytometry. OVA-specific ACAID T regs were obtained from the spleens of DO11. 10 mice with ACAID to OVA. Immunomagnetic enrichment was used to sort out CD4(+)CD25(+), and CD4(+)CD25(-) ACAID T cells before they were injected into OVA-immunized mice or examined for mRNA expression of the regulatory T-cell transcription factor Foxp3. In addition, before AC injection of OVA, systemic depletion of CD25(+) T cells was performed with injections of anti-IL-2 receptor antibody into the mice.RESULTs. OVA-specific T cells from DO11. 10 mice expressed CD25 when exposed to OVA-pulsed, TGF beta-treated APCs, even when the D011.10 T cells were depleted of CD25+ cells before their in vitro stimulation. In addition, DH was suppressed in naive mice that were injected with CD4+CD25+ or CD4(+)CD25(-) ACAID T cells. The CD44(+)CD25(+), but not the CD4(+)CD25(-), ACAID T regs expressed Foxp3. Finally, OVA induced ACAID in mice depleted of CD25(+) cells.CONCLUSIONS. Some of the CD4(+) T regs of ACAID arise from CD25(-) precursors, and the induction of ACAID is not dependent on the presence of natural CD4(+)CD25(+) T regs.