Sad S, Krishnan L, Bleackley R C, Kägi D, Hengartner H, Mosmann T R
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.
Eur J Immunol. 1997 Apr;27(4):914-22. doi: 10.1002/eji.1830270417.
Naive CD8+ T cells differentiate into distinct cytokine-secreting subsets: T helper (Th)1-like cytotoxic T cells (Tc1) and Th2-like Tc2. Although Th2 cells provide strong B cell help, we show that Tc2 cells secreting the same cytokines provide only modest B cell help for IgM production, and only when large numbers of B cells were stimulated with small numbers of Tc2 cells. Lack of effective B cell help by Tc2 cells was attributable partly to their cytotoxicity towards B cells. Both Tc1 and Tc2 cells killed small resting B cells mainly by a perforin-dependent mechanism. In contrast to normal Tc2 cells, perforin-deficient Tc2 cells failed to kill small resting B cells and induced IgM and IgG1 production, although their B cell help was significantly lower than that mediated by Th2 cells. This may be partly attributable to the ability of Tc2 but not Th2 cells to kill activated B cells even in the absence of perforin. Plate-bound anti-CD3 antibodies inhibited Tc2 killing of B cells and induced substantial immunoglobulin production. Additionally, Tc1 and Tc2 cells failed to express CD40 ligand (CD40L), whereas Th1 and Th2 cells expressed high levels of CD40L. Stimulation of Tc1 and Tc2 cells with plate-bound anti-CD3 antibodies for extended periods resulted in low-level expression of CD40L. Proliferation of small resting B cells correlated with immunoglobulin production: proliferation was promoted strongly by Th1 and Th2, weakly by normal Tc1 and Tc2, and moderately by perforin-deficient Tc1 and Tc2 cells. Thus, Tc2 cells may not contribute significantly to cognate B cell help during normal responses.
初始CD8⁺ T细胞分化为不同的细胞因子分泌亚群：辅助性T（Th）1样细胞毒性T细胞（Tc1）和Th2样Tc2细胞。尽管Th2细胞能为B细胞提供强大的辅助作用，但我们发现，分泌相同细胞因子的Tc2细胞仅能为IgM产生提供适度的B细胞辅助作用，且只有在少量Tc2细胞刺激大量B细胞时才会出现这种情况。Tc2细胞缺乏有效的B细胞辅助作用，部分原因在于它们对B细胞具有细胞毒性。Tc1和Tc2细胞主要通过穿孔素依赖性机制杀死静止的小B细胞。与正常Tc2细胞不同，穿孔素缺陷的Tc2细胞无法杀死静止的小B细胞，而是诱导IgM和IgG1产生，尽管它们的B细胞辅助作用明显低于Th2细胞介导的作用。这可能部分归因于Tc2细胞而非Th2细胞即使在没有穿孔素的情况下也能杀死活化B细胞的能力。板结合抗CD3抗体可抑制Tc2细胞对B细胞的杀伤作用，并诱导大量免疫球蛋白产生。此外，Tc1和Tc2细胞不表达CD40配体（CD40L），而Th1和Th2细胞则高水平表达CD40L。用板结合抗CD3抗体长时间刺激Tc1和Tc2细胞会导致CD40L低水平表达。静止小B细胞的增殖与免疫球蛋白产生相关：Th1和Th2细胞强烈促进增殖，正常Tc1和Tc2细胞微弱促进增殖，穿孔素缺陷的Tc1和Tc2细胞适度促进增殖。因此，在正常反应过程中，Tc2细胞可能对同源B细胞辅助作用贡献不大。
