MICROBIAL INDUCTION OF COSTIMULATORY ACTIVITY FOR CD4 T-CELL GROWTH

MICROBIAL INDUCTION OF COSTIMULATORY ACTIVITY FOR CD4 T-CELL GROWTH
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DOI:
10.1093/intimm/3.4.323
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发表时间:
1991-04-01
影响因子:
4.4
通讯作者:
JANEWAY, CA
JANEWAY, CA
中科院分区:
医学3区
文献类型:
--
作者:
LIU, Y;JANEWAY, CA

文献摘要

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抗原对初始CD 4 T细胞的激活是免疫应答启动的关键步骤;它需要T细胞受体(TCR)的连接和辅助细胞对共刺激因子的递送。 我们研究了同系辅助细胞在纯化的正常CD 4 T细胞对抗CD 3抗体作为配体的反应中的作用。 我们发现,在B细胞中,通过微生物产物如细菌脂多糖(LPS)、促有丝分裂流感病毒和合成的聚肌苷酸-聚胞苷酸(poly-I:C)作为病毒感染的模拟物,传递共刺激信号的能力是可诱导的。 LPS刺激16 h可使B细胞的共刺激活性对多聚甲醛固定产生抗性。 LPS诱导耐固定共刺激分子活性需要新的蛋白质合成,因为它被放线菌酮抑制。 使用抗-CD 45 RB mAb 16 A作为初始和记忆性CD 4 T细胞的标记物,我们表明由LPS和由聚-I:C激活的B细胞可以向初始和记忆性CD 4 T细胞提供共刺激信号。 相比之下,酵母多糖颗粒,这是已知的激活巨噬细胞在各种测定,不激活B细胞成为共刺激,但诱导这种活动的巨噬细胞。这些数据表明,各种感染因子或其成分可以诱导辅助细胞成为CD 4 T细胞的共刺激细胞。 它们被解释在光的诱导的免疫反应,抗原的特异性识别和非特异性识别的传染性病原体的两类识别的建议的作用。 这些数据支持免疫系统使用这种机制来区分感染性非自我和非感染性自我的论点。
The activation of naive CD4 T cells by antigen is a critical step in the initiation of an immune response; it requires both ligation of the T-cell receptor (TCR) and the delivery of co-stimulatory factors by accessory cells. We have examined the role of syngeneic accessory cells in the response of purified normal CD4 T cells to anti-CD3 antibody as ligand. We show that the ability to deliver co-stimulatory signals is inducible in B cells by microbial products such as bacterial lipopolysaccharide (LPS), mitogenic influenza viruses, and synthetic polyinosinic-polycytidylic acid (poly-I:C) as a mimic of viral infection. LPS stimulation for 16 h allows the co-stimulatory activity of B cells to become resistant to paraformaldehyde fixation. LPS induction of fixation-resistant co-stimulator activity requires new protein synthesis, as it is inhibited by cycloheximide. Using the anti-CD45RB mAb 16A as marker for naive and memory CD4 T cells, we show that B cells activated by LPS and by poly-I:C can provide co-stimulatory signal to both naive and memory CD4 T cells. By contrast, zymosan particles, which are known to activatemacrophages in a variety of assays, do not activate B cells to become co-stimulatory, but do induce this activity in macrophages. These data demonstrate that a variety of infectious agents or their constituents can induce accessory cells to become co-stimulatory for CD4 T cells. They are interpreted in light of a proposed role for two classes of recognition in the induction of the immune responses, specific recognition of antigens and non-specific recognition of infectious agents. These data support the contention that the immune system uses this mechanism to discriminate infectious non-self from non-infectious self.