CD4+CD25+调节性T细胞的发育与胸腺CD4-CD25+细胞关联性的探讨

目的:探讨CD4 CD25 调节性T细胞(CD4 CD25 regulatoryTcells,CD4 CD25 Tr)的发育及其与胸腺CD4-CD25 细胞的关系。方法:以流式细胞术检测小鼠从出生至发育成熟过程中,胸腺、脾脏、淋巴结和外周血中CD4 CD25 Tr比例变化,以及胸腺CD4-CD25 细胞比例变化;通过磁激活细胞分选(MACS)从小鼠淋巴结纯化CD4 CD25 T和CD4 CD25-T细胞,经CFDA-SE标记,以多种刺激形式诱导增殖。结果:小鼠出生1d到10周的发育过程中,胸腺CD4 CD25 Tr比例一直比较恒定,但在脾脏、淋巴结和外周血,随鼠龄增加而不断升高,从1d龄到1周时升高最迅速,其后的升高速度逐渐减慢,10周龄时达平台期。胸腺中CD4-CD25 细胞在出生1d的小鼠比例非常高,1d龄到1周龄期间迅速下降,10周龄时达平台期。ConA不能诱导CD4 CD25 Tr和CD4 CD25-T细胞增殖,但CD4 CD25 Tr出现一过性细胞增大;佛波醇酯加离子霉素能诱导CD4 CD25 Tr和CD4 CD25-T细胞增殖;包被的抗CD3抗体加可溶性抗CD28抗体能刺激CD4 CD25-T细胞增殖,但CD4 CD25 Tr不增殖,加入高浓度IL-2,CD4 CD25-T细胞增殖更强,CD4 CD25 Tr出现增殖。结论:胸腺CD4-CD25 细胞很有可能是CD4 CD25 Tr的前体。

Association between development of CD4+CD25+ regulatory T cells and thymus CD4-CD25+ cells

AIM: To explore the correlation between development of CD4~ CD25~ regulatory T cells (CD4~ CD25~ Tr) and thymus CD4~-CD25~ cells. METHODS: The ratios of CD4~ CD25~ regulatory T cells to CD4~ T cells in thymus, spleen, lymph node and peripheral blood of mice from birth to mature and also the ratios of CD4~-CD25~ cells to CD4~-T cells in thymus were measured by flow cytometry. Purified CD4~ CD25~ T cells and CD4~ CD25~- T cells were labeled with CFDA-SE, and then stimulated with various kinds of stimulators. RESULTS: The percentages of CD4~ CD25~ Tr in mouse spleen, lymph nodes and peripheral blood increased gradually, but not in thymus, from day one to week 10 of the age with rapid rising from day one to week 1. The percentages of CD4~-CD25~ cells in mouse thymus were quite high on day one after birth, and decreased rapidly from day one to week 1. Both CD4~ CD25~ Tr and CD4~ CD25~- T cells showed no proliferation in response to ConA, while CD4~ CD25~ Tr showed a transient enlargement of cell size. Both CD4~ CD25~ Tr and CD4~ CD25~- T cells underwent proliferation in response to PDB plus ionomycin. CD4~ CD25~- T cells, but not CD4~ CD25~ Tr, showed a proliferative response to the stimulation of coated anti-CD3 plus soluble anti-CD28 antibody, however, CD4~ CD25~ Tr showed significant proliferation and CD4~ CD25~- T cells showed a stronger response in addition of high dose of IL-2. CONCLUSION: The thymus CD4~-CD25~ cells are probably the precursor of CD4~ CD25~ Tr during cell development.