Ford A L, Britton W J, Armati P J
Centenary Institute of Cancer Medicine and Cell Biology, University of Sydney, N.S.W., Australia.
J Neuroimmunol. 1993 Mar;43(1-2):151-9. doi: 10.1016/0165-5728(93)90086-e.
Peripheral nerves are frequently damaged during infection with Mycobacterium leprae. Although Schwann cells are host for this obligate intracellular parasite, the mechanisms of immunopathology are unresolved. This study examines the ability of Lewis rat Schwann cells to present an exogenous Mycobacterium leprae protein, the heat shock protein 70 (hsp70), to antigen-specific T lymphocytes isolated from the lymph nodes of immunised rats. Secondary reactivation of hsp70-specific T lymphocytes occurred producing an antigen-specific lymphoproliferative response. This was inhibited by monoclonal antibodies against rat major histocompatibility complex (MHC) class II molecules, but not antibodies against MHC class I molecules. Coculture of Schwann cells with the M.leprae hsp70-specific T lymphocytes and antigen (MLrp70) induced the expression of MHC class II molecules on the Schwann cell's surface. Although M.leprae hsp70 is immunodominant in the host response to the bacillus, there is a high degree of homology between human and M.leprae hsp70. The M.leprae hsp70-specific T lymphocytes also recognised human hsp70 presented by Schwann cells confirming that antigenic determinants are conserved between the proteins. The ability of Schwann cells to present protein antigens in an MHC class II-restricted manner, to antigen-specific T lymphocytes involved in surveillance of the peripheral nervous system, may play an important role in the activation of an immunological reaction associated with nerve damage seen in tuberculoid leprosy.
在麻风分枝杆菌感染期间,周围神经经常受损。尽管施万细胞是这种专性细胞内寄生虫的宿主,但免疫病理学机制仍未明确。本研究检测了Lewis大鼠施万细胞将外源性麻风分枝杆菌蛋白——热休克蛋白70(hsp70)呈递给从免疫大鼠淋巴结中分离出的抗原特异性T淋巴细胞的能力。hsp70特异性T淋巴细胞发生二次激活,产生抗原特异性淋巴细胞增殖反应。这一反应受到抗大鼠主要组织相容性复合体(MHC)II类分子的单克隆抗体的抑制,但不受抗MHC I类分子抗体的抑制。施万细胞与麻风分枝杆菌hsp70特异性T淋巴细胞和抗原(MLrp70)共培养可诱导施万细胞表面MHC II类分子的表达。尽管麻风分枝杆菌hsp70在宿主对该杆菌的反应中具有免疫优势,但人hsp70与麻风分枝杆菌hsp70之间存在高度同源性。麻风分枝杆菌hsp70特异性T淋巴细胞也能识别施万细胞呈递的人hsp70,这证实了两种蛋白之间的抗原决定簇是保守的。施万细胞以MHC II类分子限制的方式将蛋白抗原呈递给参与周围神经系统监测的抗原特异性T淋巴细胞,这可能在与结核样麻风所见神经损伤相关的免疫反应激活中起重要作用。