Croft M, Swain S L
Department of Biology, University of California, San Diego, La Jolla 92093-0063.
J Immunol. 1991 Jun 15;146(12):4055-64.
The helper activity of resting T cells and in vitro generated effector T cells and the relative roles of cognate interaction, diffusible cytokines, and non-cognate T-B contact in B cell antibody responses were evaluated in a model in which normal murine CD4+ T cells (Th), activated with alloantigen-bearing APC, were used to support the growth and differentiation of unstimulated allogeneic B cells. Both "fresh" T cells, consisting of memory and naive cells, stimulated for 24 h, and "effector" T cells, derived from naive cells after 4 days of in vitro stimulation, induced the secretion of IgM, IgG3, IgG1, IgG2a, and IgA. Effector T cells were significantly better helpers of the response of small dense B cells, inducing Ig at lower numbers and inducing at optimal numbers 2- to 3-fold more Ig production than fresh T cells. The predominant isotype secreted was IgM. Supernatants derived from fresh T cell cultures contained moderate levels of IL-2, whereas those from effector cultures contained significant levels of IL-6 and IFN-gamma in addition to IL-2. The involvement of soluble factors in the B cell response was demonstrated by the ability of antibodies to the cytokines IL-2, IL-4, and IL-6 to each block Ig secretion. Antibodies to IL-5 and IFN-gamma had no effect on the T cell-induced response. Kinetic studies suggested that IL-4 acted during the initial stages of the response, whereas the inability of anti-IL-6 to block B cell proliferation suggested that IL-6 was involved in part in promoting differentiation of the B cells. The relative contributions of cognate (MHC-restricted) and bystander (MHC-unrestricted) T-B cell contact vs cytokine (non-contact)-mediated responses were assessed in a transwell culture system. The majority of the IgM, IgG3, IgG1, and IgG2a response induced by both fresh and effector T cells was dependent on cognate interaction with small, high density B cells. In contrast, a small proportion of these isotypes and most of the IgA secreted resulted from the action of IL-6 on large, presumably preactivated, B cells. The IgA response did not require cell contact or vary when fresh and effector cells were the helpers. The contribution of bystander contact in the overall antibody response to both T cell populations was minimal.(ABSTRACT TRUNCATED AT 400 WORDS)
在一个模型中评估了静息T细胞和体外产生的效应T细胞的辅助活性，以及同源相互作用、可溶性细胞因子和非同源T-B细胞接触在B细胞抗体应答中的相对作用。在该模型中，用携带同种异体抗原的抗原呈递细胞（APC）激活的正常小鼠CD4+ T细胞（Th细胞）被用来支持未受刺激的同种异体B细胞的生长和分化。经24小时刺激的由记忆细胞和初始细胞组成的“新鲜”T细胞，以及体外刺激4天后源自初始细胞的“效应”T细胞，均可诱导IgM、IgG3、IgG1、IgG2a和IgA的分泌。效应T细胞是小而致密B细胞应答的明显更好的辅助细胞，诱导产生Ig所需的细胞数量更少，在最佳细胞数量时诱导产生的Ig产量比新鲜T细胞多2至3倍。分泌的主要同种型是IgM。新鲜T细胞培养物的上清液含有中等水平的IL-2，而效应T细胞培养物的上清液除含有IL-2外，还含有高水平的IL-6和IFN-γ。针对细胞因子IL-2、IL-4和IL-6的抗体均能阻断Ig分泌，这证明了可溶性因子参与了B细胞应答。针对IL-5和IFN-γ的抗体对T细胞诱导的应答没有影响。动力学研究表明，IL-4在应答的初始阶段起作用，而抗IL-6不能阻断B细胞增殖表明IL-6部分参与促进B细胞的分化。在transwell培养系统中评估了同源（MHC限制）和旁观者（MHC非限制）T-B细胞接触与细胞因子（非接触）介导的应答的相对贡献。新鲜T细胞和效应T细胞诱导的大多数IgM、IgG3、IgG1和IgG2a应答依赖于与小而高密度B细胞的同源相互作用。相反，这些同种型中的一小部分以及分泌的大多数IgA是由IL-6作用于大的、可能已预激活的B细胞产生的。IgA应答不需要细胞接触，当新鲜T细胞和效应T细胞作为辅助细胞时也没有变化。旁观者接触对两种T细胞群体总体抗体应答的贡献最小。（摘要截短于400字）
