Kakkanaiah V N, Seth A, Nagarkatti M, Nagarkatti P S
Department of Biology, Virginia Polytechnic Institute and State University, Blacksburg.
Clin Immunol Immunopathol. 1990 Oct;57(1):148-62. doi: 10.1016/0090-1229(90)90030-t.
Recent studies have suggested the existence of two mutually exclusive subpopulations of T helper (Th) cells in the murine immune system, called Th1 which produces interleukin (IL)-2 and interferon (IFN)-gamma but not IL-4 and Th2 which secretes IL-4 and IL-5 but not IL-2. Also, functionally, Th1 cells generally activate the macrophages and mediate delayed-type hypersensitivity whereas Th2 cells provide help efficiently to B cells. In the present study, we investigated the lymphokine secretory properties of two well-characterized autoreactive (self-Ia reactive) T cell clones isolated from normal DBA/2 mice and autoimmune-susceptible MRL-lpr/lpr mice. It was observed that both the autoreactive T cell clones, following activation, produced IL-2, IL-4, and IFN-gamma. They induced hyper-Ia expression and cell proliferation in syngeneic B cells as well as activated the macrophages to exhibit tumoristatic properties. Both clones could also induce T-T network interaction in which syngeneic naive CD4+ T cells responded directly to stimulation with autoreactive T cell clones. The T-T interaction was demonstrable in 1-month-old MRL-lpr/lpr mice prior to the onset of the autoimmune disease but not in 6-month-old mice having lymphadenopathy and autoimmune disease. Unlike Th1 and Th2 cells which upon antigenic stimulation respond to exogenous IL-2 and IL-4, the autoreactive T cell clones responded only to IL-2 but not to IL-4. Our data suggest the existence of a unique subset of immunoregulatory CD4+ Th cells having the lymphokine secretory and functional properties of both the murine Th1 and Th2 subsets.
最近的研究表明，在小鼠免疫系统中存在两种相互排斥的辅助性T（Th）细胞亚群，即产生白细胞介素（IL）-2和干扰素（IFN）-γ但不产生IL-4的Th1细胞，以及分泌IL-4和IL-5但不分泌IL-2的Th2细胞。此外，在功能上，Th1细胞通常激活巨噬细胞并介导迟发型超敏反应，而Th2细胞则有效地为B细胞提供帮助。在本研究中，我们调查了从正常DBA/2小鼠和自身免疫易感的MRL-lpr/lpr小鼠中分离出的两个特征明确的自身反应性（自身Ia反应性）T细胞克隆的淋巴因子分泌特性。结果发现，这两个自身反应性T细胞克隆在激活后均产生IL-2、IL-4和IFN-γ。它们诱导同基因B细胞中Ia高表达和细胞增殖，并激活巨噬细胞以表现出抑瘤特性。两个克隆还能诱导T-T网络相互作用，其中同基因幼稚CD4+T细胞直接对自身反应性T细胞克隆的刺激作出反应。这种T-T相互作用在自身免疫疾病发作前的1月龄MRL-lpr/lpr小鼠中可以检测到，但在患有淋巴结病和自身免疫疾病的6月龄小鼠中则检测不到。与抗原刺激后对外源性IL-2和IL-4有反应的Th1和Th2细胞不同，自身反应性T细胞克隆仅对IL-2有反应，而对IL-4无反应。我们的数据表明，存在一种独特的免疫调节性CD4+Th细胞亚群，其具有小鼠Th1和Th2亚群的淋巴因子分泌和功能特性。
