Hall Bruce M, Robinson Catherine M, Plain Karren M, Verma Nirupama D, Tran Giang T, Nomura Masaru, Carter Nicole, Boyd Rochelle, Hodgkinson Suzanne J
Immune Tolerance Laboratory, Department of Medicine, Ingham Institute, University of New South Wales, Liverpool Hospital, Liverpool, NSW, Australia.
Faculty of Veterinary Sciences, University of Sydney, Cobbity, NSW, Australia.
Front Immunol. 2017 Aug 22;8:994. doi: 10.3389/fimmu.2017.00994. eCollection 2017.
Transplant tolerance induced in adult animals is mediated by alloantigen-specific CD4CD25 T cells, yet in many models, proliferation of CD4 T cells from hosts tolerant to specific-alloantigen is not impaired. To identify changes that may diagnose tolerance, changes in the patterns of proliferation of CD4, CD4CD25, and CD4CD25 T cells from DA rats tolerant to Piebald Virol Glaxo rat strain (PVG) cardiac allografts and from naïve DA rats were examined. Proliferation of CD4 T cells from both naïve and tolerant hosts was similar to both PVG and Lewis stimulator cells. In mixed lymphocyte culture to PVG, proliferation of naïve CD4CD25 T cells was greater than naïve CD4 T cells. In contrast, proliferation of CD4CD25 T cells from tolerant hosts to specific-donor PVG was not greater than CD4 T cells, whereas their response to Lewis and self-DA was greater than CD4 T cells. Paradoxically, CD4CD25 T cells from tolerant hosts did not proliferate to PVG, but did to Lewis, whereas naïve CD4CD25 T cells proliferate to both PVG and Lewis but not to self-DA. CD4CD25 T cells from tolerant, but not naïve hosts, expressed receptors for interferon (IFN)-γ and IL-5 and these cytokines promoted their proliferation to specific-alloantigen PVG but not to Lewis or self-DA. We identified several differences in the patterns of proliferation to specific-donor alloantigen between cells from tolerant and naïve hosts. Most relevant is that CD4CD25 T cells from tolerant hosts failed to proliferate or suppress to specific donor in the absence of either IFN-γ or IL-5. The proliferation to third-party and self of each cell population from tolerant and naïve hosts was similar and not affected by IFN-γ or IL-5. Our findings suggest CD4CD25 T cells that mediate transplant tolerance depend on IFN-γ or IL-5 from alloactivated Th1 and Th2 cells.
成年动物中诱导产生的移植耐受由同种异体抗原特异性CD4CD25 T细胞介导，但在许多模型中，来自对特定同种异体抗原耐受的宿主的CD4 T细胞增殖并未受损。为了确定可能诊断耐受的变化，研究了来自对花斑病毒格拉克索大鼠品系（PVG）心脏同种异体移植耐受的DA大鼠以及未接触过抗原的DA大鼠的CD4、CD4CD25和CD4CD25 T细胞的增殖模式变化。来自未接触过抗原和耐受宿主的CD4 T细胞的增殖与PVG和Lewis刺激细胞相似。在针对PVG的混合淋巴细胞培养中，未接触过抗原的CD4CD25 T细胞的增殖大于未接触过抗原的CD4 T细胞。相比之下，来自耐受宿主的CD4CD25 T细胞对特定供体PVG的增殖不大于CD4 T细胞，而它们对Lewis和自身DA的反应大于CD4 T细胞。矛盾的是，来自耐受宿主的CD4CD25 T细胞对PVG不增殖，但对Lewis增殖，而未接触过抗原的CD4CD25 T细胞对PVG和Lewis都增殖，但对自身DA不增殖。来自耐受宿主而非未接触过抗原宿主的CD4CD25 T细胞表达干扰素（IFN）-γ和IL-5的受体，这些细胞因子促进它们对特定同种异体抗原PVG的增殖，但对Lewis或自身DA不促进。我们确定了来自耐受和未接触过抗原宿主的细胞在对特定供体同种异体抗原的增殖模式上存在若干差异。最相关的是，在没有IFN-γ或IL-5的情况下，来自耐受宿主的CD4CD25 T细胞对特定供体不增殖或不抑制。来自耐受和未接触过抗原宿主的每个细胞群体对第三方和自身的增殖相似，且不受IFN-γ或IL-5的影响。我们的研究结果表明，介导移植耐受的CD4CD25 T细胞依赖于同种异体激活的Th1和Th2细胞产生的IFN-γ或IL-5。
