Marelli-Berg F M, Hargreaves R E, Carmichael P, Dorling A, Lombardi G, Lechler R I
Department of Immunology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
J Exp Med. 1996 Apr 1;183(4):1603-12. doi: 10.1084/jem.183.4.1603.
The role of endothelial cells (EC) in initiating a primary T cell response is of importance in clinical transplantation and autoimmunity since EC are the first allogeneic target encountered by the recipient's immune system and may display tissue-specific autoantigens in the context of an inflammatory response. In this study, we have investigated the antigen-presenting cell function of human umbilical vein-derived EC (HUVEC), depleted of constitutively major histocompatibility complex class II+ cells and induced to express class II molecules by interferon-gamma. The results show that HUVEC do not express B7 but can support proliferation by antigen-specific T cell clones. In contrast, they were unable to initiate a primary alloresponse using three independent HUVEC cultures and MHC class II-mismatched CD4+ T cells from eight donors. The response to HUVEC was reconstituted by trans-costimulation provided by DAP.3 transfectants expressing human B7.1. Coculture of peripheral blood T cells with EC expressing allogeneic DR molecules had markedly different effects on CD45RO+ and RA+ subsets. Subsequent reactivity of the RO+ T cells was unaffected by exposure to EC, indicating a neutral encounter. In contrast, culture with DR+ EC induced allospecific nonresponsiveness in RA+ T cells.
内皮细胞(EC)在引发原发性T细胞应答中的作用在临床移植和自身免疫中具有重要意义,因为EC是受体免疫系统遇到的首个同种异体靶标,并且在炎症反应的背景下可能展示组织特异性自身抗原。在本研究中,我们研究了人脐静脉来源的EC(HUVEC)的抗原呈递细胞功能,这些细胞去除了组成性主要组织相容性复合体II类阳性细胞,并通过γ干扰素诱导表达II类分子。结果表明,HUVEC不表达B7,但能支持抗原特异性T细胞克隆的增殖。相比之下,使用来自8名供体的三种独立的HUVEC培养物和MHC II类不匹配的CD4 + T细胞,它们无法引发原发性同种异体反应。对HUVEC的反应通过表达人B7.1的DAP.3转染体提供的反式共刺激得以重建。外周血T细胞与表达同种异体DR分子的EC共培养对CD45RO +和RA +亚群有明显不同的影响。RO + T细胞随后的反应性不受与EC接触的影响,表明是中性相遇。相比之下,与DR + EC共培养在RA + T细胞中诱导同种异体特异性无反应性。