Kotani H, Mitsuya H, Benson E, James S P, Strober W
Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
J Immunol. 1988 Jun 15;140(12):4167-72.
Previously it was demonstrated that the human autoreactive CD4+ T cell clone MTC-4 is bifunctional, having the capacity to augment differentiation of autologous B cells into Ig-secreting cells in the absence of PWM and the capacity to suppress such differentiation in the presence of PWM. In the present study it was shown that these two functions of MTC-4 are mediated by distinctly different mechanisms. In the presence of autologous class II MHC Ag, MTC-4 releases one or more non-MHC-restricted soluble factors which stimulate B cell differentiation. The helper factors are different from IL-2, and act on both resting (small) and activated (large) B cells. The suppressor function of MTC-4 cells is elicited when MTC-4 cells are co-cultured with autologous non-T cells preincubated with PWM for 4 h, but not with non-T cells preincubated with PWM for 24 h; thus, activated autologous non-T cells have a transient capacity to induce MTC-4 suppressor function. Induction of MTC-4 suppressor activity is not associated with increased proliferation of MTC-4 and is mediated by low numbers of these cells. Unlike helper function, MTC-4 suppression of Ig synthesis can occur late in B cell cultures, and MTC-4 suppresses Ig production by autologous B cells, but not by allogeneic B cells. Finally, in co-cultures with activated autologous non-T cells and allogeneic B cells, MTC-4 can simultaneously produce helper factors that augment Ig synthesis by allogeneic B cells and suppress Ig synthesis by autologous B cells. In summary, exposure of MTC-4 to autologous non-T cells causes release of non-MHC-restricted factors which augment Ig production by both resting and activated autologous B cells, whereas exposure of MTC-4 to recently activated B cells causes MTC-4 to express the additional function of directly suppressing Ig production by differentiated autologous B cells. Thus autoreactive T cells may be uniquely suited to regulate Ig production.
先前已证明，人类自身反应性CD4+ T细胞克隆MTC-4具有双重功能，在无PWM的情况下有能力增强自体B细胞向分泌Ig细胞的分化，而在有PWM的情况下有能力抑制这种分化。在本研究中表明，MTC-4的这两种功能是由截然不同的机制介导的。在有自体II类MHC Ag存在的情况下，MTC-4释放一种或多种非MHC限制的可溶性因子，这些因子刺激B细胞分化。辅助因子不同于IL-2，作用于静止（小）和活化（大）B细胞。当MTC-4细胞与预先用PWM孵育4小时的自体非T细胞共培养时，MTC-4细胞的抑制功能被诱导，但与预先用PWM孵育24小时的非T细胞共培养时则不会；因此，活化的自体非T细胞具有诱导MTC-4抑制功能的短暂能力。MTC-4抑制活性的诱导与MTC-4增殖增加无关，且由少量这些细胞介导。与辅助功能不同，MTC-4对Ig合成的抑制可发生在B细胞培养后期，且MTC-4抑制自体B细胞而非同种异体B细胞的Ig产生。最后，在与活化的自体非T细胞和同种异体B细胞的共培养中，MTC-4可同时产生辅助因子，增强同种异体B细胞的Ig合成并抑制自体B细胞的Ig合成。总之，MTC-4暴露于自体非T细胞会导致释放非MHC限制的因子，增强静止和活化的自体B细胞的Ig产生，而MTC-4暴露于最近活化的B细胞会使MTC-4表达直接抑制分化的自体B细胞的Ig产生的额外功能。因此，自身反应性T细胞可能特别适合调节Ig产生。
