The expression of CD4 and CD8 molecules conditions the behavior of V beta + murine thymocytes upon superantigenic challenge.

Thymus Pub Date : 1997-01-01
A Fattorossi, S Baschieri, C Ferlini, G Doria
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Abstract

We investigated the capacity of the Staphylococcal enterotoxin (SE) B, a superantigen (SAg) specific for TCR V beta domain, to modulate V beta 8+ thymocytes selection in adult mice. Thymocytes were collected at various time intervals after SEB injection (10 and 100 micrograms) and V beta 8+ modulation was analysed by three color flow cytometry. SEB failed to affect V beta 8+ thymocytes comprised in the less mature compartments, namely, CD4+8+ and CD4-CD8-, whereas it selectively affected V beta 8+CD4+8+ (downward modulation) and V beta 8+CD4-8+ thymocytes (upward modulation). The different response to SEB challenge between CD4+8- and CD4-8+ thymocytes appeared dependent on the CD4/MHC class II interaction, as V beta 8+CD4-8+ thymocytes carrying a transgenic CD4 molecule capable of interacting with MHC class II showed the same response of V beta 8+CD4+8- thymocytes. At variance with thymocytes, however, V beta 8+CD4+8- and V beta 8+CD4-8+ splenic T lymphocytes responded to SAg challenge in identical manner (upward modulation) highlighting the importance of maturation status and/or microenvironment in SAg response. V beta 8+ thymocytes remaining in the thymus were assessed for their capacity to respond to a SAg challenge. Thus, thymocytes were obtained at various time intervals after SEB injection and cultured in the presence of SEB or SEA, a Sag specific for V beta 10 as control. A reduced mitotic response to SEB but not to SEA was noticed irrespective of the number of V beta 8+ responding cells present in culture. It is concluded that SAgs affect TCR specific thymocytes by conditioning their redistribution and inducing an anergic status.

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CD4和CD8分子的表达决定了V β +小鼠胸腺细胞在超抗原攻击下的行为。
我们研究了葡萄球菌肠毒素(SE) B,一种TCR V β结构域特异性的超抗原(SAg),在成年小鼠中调节V β 8+胸腺细胞选择的能力。注射SEB(10和100微克)后,在不同的时间间隔收集胸腺细胞,用三色流式细胞术分析V β 8+的调节。SEB不能影响不成熟腔室中组成的V β 8+胸腺细胞,即CD4+8+和CD4- cd8 -,而有选择性地影响V β 8+CD4+8+(向下调节)和V β 8+CD4-8+胸腺细胞(向上调节)。CD4+8-和CD4-8+胸腺细胞对SEB攻击的不同反应似乎依赖于CD4/MHC II类相互作用,因为携带能够与MHC II类相互作用的转基因CD4分子的V β 8+CD4-8+胸腺细胞表现出与V β 8+CD4+8-胸腺细胞相同的反应。然而,与胸腺细胞不同的是,V β 8+CD4+8-和V β 8+CD4-8+脾T淋巴细胞以相同的方式(向上调节)对SAg反应作出反应,这突出了成熟状态和/或微环境在SAg反应中的重要性。我们评估了存留在胸腺中的V β 8+胸腺细胞对SAg挑战的反应能力。因此,注射SEB后在不同的时间间隔获得胸腺细胞,并在SEB或SEA (V β 10特异性Sag)存在下培养作为对照。无论培养中V β 8+反应细胞的数量如何,对SEB的有丝分裂反应减少,但对SEA的反应没有减少。综上所述,sag通过调节TCR特异性胸腺细胞的再分配和诱导无能状态来影响TCR特异性胸腺细胞。
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