Larché M, Lamb J R, Ritter M A
Department of Immunology, Royal Postgraduate Medical School, Hammersmith Hospital, London, U.K.
Immunology. 1988 May;64(1):101-5.
T-cell differentiation is known to take place in the thymus, but the precise mechanisms involved remain unresolved. In order to analyse the role of the thymic microenvironment in thymocyte maturation and generation of the T-cell repertoire, we have raised monoclonal antibodies (mAb) to thymic stromal cells, and with these can recognize, in the non-lymphoid component of the thymus, several antigenically distinct compartments. One mAb, MR6, binds to both the cortical epithelium and medullary macrophages/dendritic (M phi/DC) cells in sections of the human thymus. Recently, the molecule detected by MR6 has also been detected at low levels on the surface of T lymphocytes. We now report that this molecule has a relative molecular mass of 145,000 (p145-MR6) and that this appears to be the same for both thymic lymphocytes and stromal cells. Functional studies show that mAb MR6 inhibits both the antigen-specific and the IL-2-induced proliferative response of MHC class II-restricted cloned helper T cells and peripheral blood mononuclear cells (PBMC). These results suggest that the molecule to which mAb MR6 binds could be responsible for the inhibition of T-cell proliferation to self-antigens, and hence may be involved in tolerance induction and MHC restriction.
已知T细胞分化发生在胸腺中，但其中涉及的精确机制仍未得到解决。为了分析胸腺微环境在胸腺细胞成熟和T细胞库产生中的作用，我们制备了针对胸腺基质细胞的单克隆抗体（mAb），利用这些抗体可以识别胸腺非淋巴成分中几个抗原性不同的区室。一种单克隆抗体MR6，在人胸腺切片中与皮质上皮细胞和髓质巨噬细胞/树突状（M phi/DC）细胞都结合。最近，在T淋巴细胞表面也检测到了由MR6检测到的分子，但水平较低。我们现在报告，该分子的相对分子质量为145,000（p145-MR6），胸腺淋巴细胞和基质细胞的该分子似乎相同。功能研究表明，单克隆抗体MR6抑制MHC II类限制性克隆辅助性T细胞和外周血单个核细胞（PBMC）的抗原特异性和IL-2诱导的增殖反应。这些结果表明，单克隆抗体MR6所结合的分子可能是抑制T细胞对自身抗原增殖的原因，因此可能参与了耐受性诱导和MHC限制。
