Dimitriu-Bona A, Fillit H
Department of Geriatrics and Adult Development, Mount Sinai Medical Center, New York, New York 10029-6574.
Cell Immunol. 1993 Sep;150(2):321-32. doi: 10.1006/cimm.1993.1200.
As in human scleroderma, tight skin (TSK/+) mice develop cutaneous hyperplasia with over-production of extracellular matrix, including collagen and proteoglycans, associated with autoimmunity to a number of autoantigens. The present study investigated the presence of cellular autoimmunity to basement membrane heparan sulfate proteoglycan (HSPG) in diseased TSK/+mice and their nondiseased littermates, pallid mice (+/pa). Lymphocyte proliferative responses to specific HSPG antigens, including intact HSPG, HSPG protein core (P. Core), and the glycosaminoglycan heparan sulfate (HS) were studied. Splenocytes from young TSK and control pallid mice reacted weakly to intact HSPG and HSPG P. Core antigens and did not respond to HS. However, lymphocytes from old TSK mice were reactive with HSPG and P. Core and demonstrated a de novo response to HS. The proliferative response to intact HSPG and HSPG P. Core in TSK mice was T cell dependent, but the response to HS was T cell independent. The T cell-dependent response was mediated by the CD4-positive subset and required the participation of class II major histocompatibility complex molecules. Cellular autoimmunity to HSPG, a critical cell surface and extracellular matrix component, may play a role in the disease suffered by TSK mice. Further studies are necessary to determine the mechanisms which link autoimmunity to HSPG with the pathology seen in TSK mice, particularly the overproduction of extracellular matrix and fibrosis.
与人类硬皮病一样，紧皮（TSK/+）小鼠会出现皮肤增生，细胞外基质过度产生，包括胶原蛋白和蛋白聚糖，同时伴有针对多种自身抗原的自身免疫反应。本研究调查了患病的TSK/+小鼠及其未患病的同窝小鼠——苍白小鼠（+/pa）中，针对基底膜硫酸乙酰肝素蛋白聚糖（HSPG）的细胞自身免疫情况。研究了淋巴细胞对特定HSPG抗原的增殖反应，包括完整的HSPG、HSPG蛋白核心（P. Core）和糖胺聚糖硫酸乙酰肝素（HS）。来自年轻TSK小鼠和对照苍白小鼠的脾细胞对完整的HSPG和HSPG P. Core抗原反应较弱，对HS无反应。然而，来自老年TSK小鼠的淋巴细胞对HSPG和P. Core有反应，并对HS表现出全新的反应。TSK小鼠对完整HSPG和HSPG P. Core的增殖反应依赖于T细胞，但对HS的反应不依赖T细胞。T细胞依赖性反应由CD4阳性亚群介导，需要II类主要组织相容性复合体分子的参与。对HSPG（一种关键的细胞表面和细胞外基质成分）的细胞自身免疫可能在TSK小鼠所患疾病中起作用。有必要进一步研究将针对HSPG的自身免疫与TSK小鼠中所见病理联系起来的机制，特别是细胞外基质的过度产生和纤维化。
