小鼠大肠黏膜CD8 + 细胞的异质性和偏向性T细胞受体α/β库：对功能状态的影响
Heterogeneity and biased T cell receptor alpha/beta repertoire of mucosal CD8+ cells from murine large intestine: implications for functional state.
作者信息
Ibraghimov A R, Lynch R G
机构信息
Department of Pathology, University of Iowa College of Medicine, Iowa City 52242.
出版信息
J Exp Med. 1994 Aug 1;180(2):433-44. doi: 10.1084/jem.180.2.433.
Up to 90% of CD8+ intraepithelial lymphocytes (IEL) of the murine large intestine (LI) belong to the alpha/beta T cell lineage and consist of two subsets. One subset expresses both alpha and beta subunits of the CD8 coreceptor, and is uniformly Thy1+, CD5+, B220-, CD2+, CD28+. The CD8 alpha+beta+ LI-IEL exclude self-reacting V beta structures, and readily proliferate in vivo in response to T cell receptor-mediated stimuli. The CD8 alpha+beta- subset of TCR-alpha/beta+ LI-IEL is Thy1-/+, CD5-, B220+, CD2+/-, and CD28-. It contains cells with potentially self-reacting V beta s and is responsive in vivo to high doses of anti-TCR-alpha/beta monoclonal antibody (mAb), but not to bacterial superantigens. Both subsets are abundant in LI-IEL of old nude mice, and CD8 alpha+beta+ LI-IEL in nude mice undergo the same V beta deletions as in euthymic mice of the same background. Both subsets express the intestinal T cell-specific integrin alpha M290 beta 7, known to be a homing receptor for IEL. Unusually high proportions of CD69+ cells within both subsets indicate chronic activation. The proportions of CD69+ and alpha M290 beta 7+ cells within the CD8 alpha+beta+ subset increase with age, probably due to constant antigenic challenge. We propose that CD8 alpha+beta+ and CD8 alpha+beta- subsets of LI-IEL permanently reside in LI and represent a lineage different from spleen and lymph node CD8+ T cells. The CD8 alpha+beta+ undergoes negative selection, and is responsive to TCR-mediated stimuli. The CD8 alpha+beta- subset of LI-IEL is a subject of distinct selection mechanisms, and has low responsiveness to TCR-mediated stimuli.
小鼠大肠（LI）中高达90%的CD8⁺上皮内淋巴细胞（IEL）属于α/β T细胞谱系，由两个亚群组成。一个亚群表达CD8共受体的α和β亚基，均为Thy1⁺、CD5⁺、B220⁻、CD2⁺、CD28⁺。CD8α⁺β⁺ LI - IEL排除自身反应性Vβ结构，并在体内对T细胞受体介导的刺激容易增殖。TCR - α/β⁺ LI - IEL的CD8α⁺β⁻亚群为Thy1⁻/⁺、CD5⁻、B220⁺、CD2⁺/⁻和CD28⁻。它包含具有潜在自身反应性Vβ的细胞，并且在体内对高剂量抗TCR - α/β单克隆抗体（mAb）有反应，但对细菌超抗原无反应。两个亚群在老年裸鼠的LI - IEL中都很丰富，并且裸鼠中的CD8α⁺β⁺ LI - IEL与相同背景的正常胸腺小鼠经历相同的Vβ缺失。两个亚群都表达肠道T细胞特异性整合素αM290β7，已知它是IEL的归巢受体。两个亚群中异常高比例的CD69⁺细胞表明慢性激活。CD8α⁺β⁺亚群中CD69⁺和αM290β7⁺细胞的比例随年龄增加，可能是由于持续的抗原刺激。我们提出，LI - IEL的CD8α⁺β⁺和CD8α⁺β⁻亚群永久驻留在LI中，代表不同于脾脏和淋巴结CD8⁺ T细胞的一个谱系。CD8α⁺β⁺经历阴性选择，并对TCR介导的刺激有反应。LI - IEL的CD8α⁺β⁻亚群是独特选择机制的对象，并且对TCR介导的刺激反应性低。
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