Issekutz T B
Department of Pediatrics, Dalhousie University, Izaak Walton Killam Hospital for Children, Halifax, Nova Scotia, Canada.
J Immunol. 1992 Nov 15;149(10):3394-402.
Lymphocyte function-associated Ag-1 (LFA-1) or CD11a/CD18 mediates lymphocyte adhesion to cultured vascular endothelial cells (EC). Thus, LFA-1 likely plays a major role in lymphocyte migration out of the blood, but there is little information on this in vivo. Small peritoneal exudate lymphocytes (sPEL) and lymph node (LN) lymphoblasts adhere to cytokine-activated EC and preferentially migrate to cutaneous inflammatory sites. The role of LFA-1 in the adherence and in vivo migration of these T cells was determined. Because of a lack of anti-rat LFA-1, mAb were prepared to rat T cells. One mAb, TA-3, inhibited homotypic aggregation; T cell proliferation to Ag, alloantigens, and mitogens; stained all leukocytes; and immunoprecipitated 170- and 95-kDa polypeptides from lymphocytes and neutrophils. TA-3 binding to lymphocytes also required Ca2+, but not Mg2+. Thus, TA-3 appears to react with rat LFA-1. TA-3 inhibited spleen T cell adhesion to unstimulated EC by 30% and to IFN-gamma, TNF-alpha, IL-1 alpha, and LPS stimulated EC by 50 to 60% but inhibited sPEL EC adhesion by only 10%. TA-3 also strongly inhibited anti-CD3-stimulated LN T cell adherence. The migration of spleen T cells to delayed-type hypersensitivity and skin sites injected with LPS, poly I:C, IFN-gamma, IFN-alpha/beta, and TNF was inhibited by 72 to 88% by TA-3, and was decreased by 50% to peripheral LN. TA-3 caused less but still 50 to 60% inhibition of sPEL migration to inflamed skin. Lymphoblast migration to skin was inhibited 40 to 80% and to PLN by 30%. Migration of lymphocytes from all sources to mesenteric LN was inhibited by 32 to 60%. In conclusion, LFA-1 mediates much of the adherence of spleen T cells and lymphoblasts to EC in vitro, most of the migration of these cells to dermal inflammation and about 50% of the homing of LN and spleen T cells to peripheral and mesenteric LN. sPEL are less dependent on LFA-1 for adhesion to EC in vitro and for migration to inflamed skin and LN in vivo.
淋巴细胞功能相关抗原-1（LFA-1）或CD11a/CD18介导淋巴细胞与培养的血管内皮细胞（EC）的黏附。因此，LFA-1可能在淋巴细胞从血液中迁移过程中起主要作用，但关于其在体内的情况知之甚少。小腹腔渗出淋巴细胞（sPEL）和淋巴结（LN）淋巴母细胞可黏附于细胞因子激活的EC，并优先迁移至皮肤炎症部位。研究了LFA-1在这些T细胞黏附和体内迁移中的作用。由于缺乏抗大鼠LFA-1，制备了针对大鼠T细胞的单克隆抗体（mAb）。一种单克隆抗体TA-3可抑制同型聚集；T细胞对抗原、同种异体抗原和丝裂原的增殖反应；可对所有白细胞进行染色；并能从淋巴细胞和中性粒细胞中免疫沉淀出170 kDa和95 kDa的多肽。TA-3与淋巴细胞的结合也需要Ca2+，但不需要Mg2+。因此，TA-3似乎与大鼠LFA-1发生反应。TA-3可使脾T细胞与未刺激的EC的黏附减少30%，与干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1α（IL-1α）和脂多糖（LPS）刺激的EC的黏附减少50%至60%，但仅使sPEL与EC的黏附减少10%。TA-3也强烈抑制抗CD3刺激的LN T细胞的黏附。TA-3可使脾T细胞向迟发型超敏反应部位以及注射LPS、多聚肌苷酸:胞苷酸（poly I:C）、IFN-γ、干扰素-α/β（IFN-α/β）和TNF的皮肤部位的迁移减少72%至88%，并使向周围LN的迁移减少50%。TA-3对sPEL向炎症皮肤的迁移的抑制作用较小，但仍为50%至60%。淋巴母细胞向皮肤的迁移减少40%至80%，向腹股沟淋巴结（PLN）的迁移减少30%。来自所有来源的淋巴细胞向肠系膜LN的迁移减少32%至60%。总之，LFA-1介导了体外脾T细胞和淋巴母细胞与EC的大部分黏附，这些细胞向皮肤炎症部位的大部分迁移，以及LN和脾T细胞向周围和肠系膜LN归巢的约50%。sPEL在体外与EC黏附以及在体内向炎症皮肤和LN迁移方面对LFA-1的依赖性较小。
