Matesic D, Valujskikh A, Pearlman E, Higgins A W, Gilliam A C, Heeger P S
Department of Medicine, Cleveland Veterans' Affairs Medical Center, OH 44106, USA.
J Immunol. 1998 Nov 15;161(10):5236-44.
Allograft rejection has been associated with detection of the type 1 lymphokines, IFN-gamma and IL-2. The role of type 2 cytokines (IL-4 and IL-5) remains controversial, as is whether alloreactive CD4+ and CD8+ T cells behave similarly when exposed to type 2 cytokine-enhancing manipulations. We studied the characteristics of alloreactive CD4+ and CD8+ T cells before and after type 2 immune deviation induced by IL-4 plus anti-IFN-gamma Ab. Alloreactive T cells from naive mice were low in frequency, produced only IL-2, and were predominantly CD4+, while alloreactive T cells from allograft-primed mice were high in frequency, produced IFN-gamma, IL-2, and IL-4, and were predominantly CD8+. Type 2 immune deviation of allospecific CD4+ T cells resulted in IL-4 and IL-5 production without IFN-gamma, consistent with unipolar type 2 immunity. These T cells mediated delayed-type hypersensitivity, but not cytotoxicity. Under identical type 2 cytokine-inducing conditions, allospecific CD8+ T cells were primed to become IL-4, IL-5, and IFN-gamma producers, and exhibited cytotoxicity, but not classic delayed-type hypersensitivity. Adoptive transfer of either cell population into SCID recipients of allogeneic skin resulted in graft rejection, with stable allospecific type 2 cytokine production in vivo. Adoptive transfer of the IL-4/IL-5-producing CD4+ T cells, but not the CD8+ T cells, induced a distinct histopathology characterized by marked eosinophilic infiltration of the skin. We conclude that type 2 immune deviation has differential effects on CD4+ and CD8+ T cells and results in emergence of alternate effector mechanisms capable of destroying allografts.
同种异体移植排斥反应与1型淋巴细胞因子（IFN-γ和IL-2）的检测有关。2型细胞因子（IL-4和IL-5）的作用仍存在争议，同种反应性CD4+和CD8+ T细胞在暴露于增强2型细胞因子的操作时是否表现相似也存在争议。我们研究了IL-4加抗IFN-γ抗体诱导2型免疫偏离前后同种反应性CD4+和CD8+ T细胞的特征。来自未接触过抗原的小鼠的同种反应性T细胞频率较低，仅产生IL-2，且主要为CD4+，而来自同种异体移植致敏小鼠的同种反应性T细胞频率较高，产生IFN-γ、IL-2和IL-4，且主要为CD8+。同种特异性CD4+ T细胞的2型免疫偏离导致产生IL-4和IL-5而无IFN-γ，这与单极性2型免疫一致。这些T细胞介导迟发型超敏反应，但不介导细胞毒性。在相同的2型细胞因子诱导条件下，同种特异性CD8+ T细胞被诱导产生IL-4、IL-5和IFN-γ，并表现出细胞毒性，但不表现出典型的迟发型超敏反应。将任一细胞群体过继转移到同种异体皮肤的SCID受体中均导致移植排斥反应，体内同种特异性2型细胞因子产生稳定。过继转移产生IL-4/IL-5的CD4+ T细胞而非CD8+ T细胞可诱导一种独特的组织病理学特征，即皮肤出现明显的嗜酸性粒细胞浸润。我们得出结论，2型免疫偏离对CD4+和CD8+ T细胞有不同影响，并导致能够破坏同种异体移植物的替代效应机制的出现。
