Hirohata S, Shinohara S
2nd Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Cell Immunol. 1993 Sep;150(2):257-68. doi: 10.1006/cimm.1993.1195.
Although human T cells have been shown to exert effects of both help and suppression on B cells, the precise sequelae for these different effects have not yet been delineated. The present study therefore examined in detail the functions of human peripheral blood T cells activated for various periods by immobilized anti-CD3 to modulate B cell responses. CD4+ (CD45RA+ or CD45RA-) or CD8+ (CD45RA+ or CD45RA-) T cell subsets were cultured in wells with immobilized anti-CD3 for as long as 20 days. At various periods of time, these activated T cells were harvested and cocultured with either fresh resting B cells or preactivated B cells. CD4+ and CD8+ T cells, irrespective of their expression of the CD45RA molecule, were able to stimulate resting B cells to express transferrin receptor (CD71) and IL-2 receptor (CD25) up to 17 days after activation with immobilized anti-CD3, although CD8+ but not CD4+ T cell subsets appeared to become less potent in stimulating resting B cells after 17 days of activation. By contrast, these CD4+ and CD8+ T cell subsets activated by immobilized anti-CD3 suppressed the maturation of the B cells preactivated with anti-CD3-stimulated CD4+ T cells, at the same time as when they provided help for resting B cells. The suppression, but not the help, was abrogated by treatment of the T cells with mitomycin C up to 13 days after activation. The suppression was not abrogated by addition of exogenous IL-2, irrespective of the length of stimulation of suppressor-effector T cells. These results indicate that human activated T cells can provide help and suppression simultaneously, irrespective of their phenotypes. Moreover, the data suggest that the state of activation of B cells might be important in determining the functions of the activated T cells.
尽管已表明人类T细胞对B细胞具有辅助和抑制作用,但这些不同作用的确切后果尚未明确。因此,本研究详细检测了通过固定化抗CD3激活不同时长的人外周血T细胞调节B细胞反应的功能。将CD4 +(CD45RA +或CD45RA -)或CD8 +(CD45RA +或CD45RA -)T细胞亚群在含有固定化抗CD3的孔中培养长达20天。在不同时间点,收集这些活化的T细胞,并与新鲜的静息B细胞或预活化的B细胞共培养。无论其CD45RA分子的表达如何,CD4 +和CD8 + T细胞在被固定化抗CD3激活后长达17天能够刺激静息B细胞表达转铁蛋白受体(CD71)和IL - 2受体(CD25),尽管在激活17天后,CD8 +而不是CD4 + T细胞亚群刺激静息B细胞的能力似乎变弱。相比之下,这些被固定化抗CD3激活的CD4 +和CD8 + T细胞亚群在为静息B细胞提供辅助的同时,抑制了由抗CD3刺激的CD4 + T细胞预活化的B细胞的成熟。在用丝裂霉素C处理T细胞后,激活后长达13天,抑制作用被消除,而辅助作用未被消除。无论抑制效应T细胞的刺激时长如何,添加外源性IL - 2均不能消除抑制作用。这些结果表明,人类活化的T细胞无论其表型如何,均可同时提供辅助和抑制作用。此外,数据表明B细胞的激活状态可能在决定活化T细胞的功能中起重要作用。