Hiroi T, Fujihashi K, McGhee J R, Kiyono H
Department of Oral Biology, University of Alabama at Birmingham Medical Center 35294-2170, USA.
Eur J Immunol. 1995 Oct;25(10):2743-51. doi: 10.1002/eji.1830251005.
Currently only limited information is available as to why dominant IgA isotype responses are supported by mucosal T cells in effector tissues. To address this issue directly, gamma delta and alpha beta T cells were isolated from the submandibular gland (SMG) of mice as an example of mucosal effector tissues. Freshly isolated CD3+ T cells from this tissue contained relatively high numbers of activated cells [approximately 10% interleukin-2 receptor (IL-2R)+ cells and 15% of cells in cycle stages S and G2 + M], of which 25% and 75% were gamma delta and alpha beta T cells, respectively. The cytokine-specific quantitative reverse transcriptase-polymerase chain reaction and enzyme-linked immunospot analyses revealed that, although both gamma delta and alpha beta T cells were capable of producing an array of Th1 or Th2 cytokines following stimulation via the T cell receptor-CD3 complex, these mucosal T cells were mainly committed to IL-5 and IL-6 expression in vivo (Th2 type). Both freshly isolated gamma delta and alpha beta T cells expressed mRNA and contained IL-5 and IL-6 spot-forming cells (SFC); however, only the latter exhibited high mRNA levels and SFC for a Th1 cytokine (interferon-gamma). Taken together, the results show that freshly isolated CD3+ T cells from SMG contain activated gamma delta and alpha beta T cells which are programmed to produce IL-5 and IL-6. Thus, SMG, an example of an IgA effector tissue, can be characterized as a Th2-dominant site. However, although both gamma delta and alpha beta T cells express cytokine profiles consistent with a Th2 phenotype, only the latter subset with a CD4+ CD8- phenotype provided effective help for mucosal B cell responses in vitro.
目前,关于效应组织中的黏膜T细胞为何支持占主导地位的IgA同种型应答,仅有有限的信息。为了直接解决这个问题,从小鼠下颌下腺(SMG)分离出γδ和αβ T细胞,作为黏膜效应组织的一个例子。从该组织新鲜分离的CD3⁺ T细胞含有相对大量的活化细胞[约10%的白细胞介素-2受体(IL-2R)⁺细胞和15%处于S期和G2 + M期的细胞周期阶段的细胞],其中分别有25%和75%是γδ和αβ T细胞。细胞因子特异性定量逆转录聚合酶链反应和酶联免疫斑点分析显示,尽管γδ和αβ T细胞在通过T细胞受体-CD3复合物刺激后都能够产生一系列Th1或Th2细胞因子,但这些黏膜T细胞在体内主要倾向于表达IL-5和IL-6(Th2型)。新鲜分离的γδ和αβ T细胞都表达mRNA并含有IL-5和IL-6斑点形成细胞(SFC);然而,只有后者显示出Th1细胞因子(干扰素-γ)的高mRNA水平和SFC。综上所述,结果表明,从SMG新鲜分离的CD3⁺ T细胞含有活化的γδ和αβ T细胞,它们被编程产生IL-5和IL-6。因此,作为IgA效应组织例子的SMG可被表征为以Th2为主导的部位。然而,尽管γδ和αβ T细胞都表达与Th2表型一致的细胞因子谱,但只有具有CD4⁺ CD8⁻表型的后者亚群在体外为黏膜B细胞应答提供了有效的帮助。