Hall Bruce M, Plain Karren M, Tran Giang T, Verma Nirupama D, Robinson Catherine M, Nomura Masaru, Boyd Rochelle, Hodgkinson Suzanne J
Immune Tolerance Group, Faculty of Medicine, University of New South Wales Australia, Sydney, NSW, Australia; Ingham Institute, Liverpool, NSW, Australia.
Immune Tolerance Group, Faculty of Medicine, University of New South Wales Australia, Sydney, NSW, Australia; Ingham Institute, Liverpool, NSW, Australia.
Transpl Immunol. 2017 Aug;43-44:33-41. doi: 10.1016/j.trim.2017.06.003. Epub 2017 Jun 23.
CD4T cells mediate antigen-specific allograft tolerance, but die in culture without activated lymphocyte derived cytokines. Supplementation of the media with cytokine rich supernatant, from ConA activated spleen cells, preserves the capacity of tolerant cells to transfer tolerance and suppress rejection. rIL-2 or rIL-4 alone are insufficient to maintain these cells, however. We observed that activation of naïve CD4CD25FOXP3Treg with alloantigen and the Th2 cytokine rIL-4 induces them to express interleukin-5 specific receptor alpha (IL-5Rα) suggesting that IL-5, a Th2 cytokine that is produced later in the immune response may promote tolerance mediating Treg. This study examined if recombinant IL-5(rIL-5) promoted survival of tolerant CD4, especially CD4CD25T cells. CD4T cells, from DA rats tolerant to fully allogeneic PVG heart allografts surviving over 100days without on-going immunosuppression, were cultured with PVG alloantigen and rIL-5. The ability of these cells to adoptively transfer tolerance to specific-donor allograft and suppress normal CD4T cell mediated rejection in adoptive DA hosts was examined. Tolerant CD4CD25T cells' response to rIL-5 and expression of IL-5Rα was also assessed. rIL-5 was sufficient to promote transplant tolerance mediating CD4T cells' survival in culture with specific-donor alloantigen. Tolerant CD4T cells cultured with rIL-5 retained the capacity to transfer alloantigen-specific tolerance and inhibited naïve CD4T cells' capacity to effect specific-donor graft rejection. rIL-5 promoted tolerant CD4CD25T cells' proliferation in vitro when stimulated with specific-donor but not third-party stimulator cells. Tolerant CD4CD25T cells expressed IL-5Rα. This study demonstrated that IL-5 promoted the survival of alloantigen-specific CD4CD25T cells that mediate transplant tolerance.
CD4 T细胞介导抗原特异性同种异体移植耐受，但在无活化淋巴细胞衍生细胞因子的培养中会死亡。用来自刀豆蛋白A激活的脾细胞的富含细胞因子的上清液补充培养基，可保留耐受细胞传递耐受和抑制排斥反应的能力。然而，单独的重组白细胞介素-2（rIL-2）或重组白细胞介素-4（rIL-4）不足以维持这些细胞。我们观察到，用同种异体抗原和Th2细胞因子rIL-4激活初始CD4 CD25 FOXP3 Treg会诱导它们表达白细胞介素-5特异性受体α（IL-5Rα），这表明白细胞介素-5（一种在免疫反应后期产生的Th2细胞因子）可能促进介导耐受的调节性T细胞（Treg）。本研究检测了重组白细胞介素-5（rIL-5）是否能促进耐受的CD4细胞，尤其是CD4 CD25 T细胞的存活。将来自对完全同种异体PVG心脏移植耐受超过100天且未进行持续免疫抑制的DA大鼠的CD4 T细胞，与PVG同种异体抗原和rIL-5一起培养。检测这些细胞将耐受过继转移至特异性供体同种异体移植以及抑制过继转移的DA宿主中正常CD4 T细胞介导的排斥反应的能力。还评估了耐受的CD4 CD25 T细胞对rIL-5的反应以及IL-5Rα的表达。rIL-5足以促进介导移植耐受的CD4 T细胞在与特异性供体同种异体抗原共培养时的存活。用rIL-5培养的耐受CD4 T细胞保留了传递同种异体抗原特异性耐受的能力，并抑制了初始CD4 T细胞对特异性供体移植物排斥反应的作用能力。当用特异性供体而非第三方刺激细胞刺激时，rIL-5促进了耐受的CD4 CD25 T细胞在体外的增殖。耐受的CD4 CD25 T细胞表达IL-5Rα。本研究表明，白细胞介素-5促进了介导移植耐受的同种异体抗原特异性CD4 CD25 T细胞的存活。
