Role Of LFA-1-mediated T Lymphocyte Activation And Differentiation In Experimental Autoimmune Encephalomyelitis

Multiple sclerosis (MS) is a typical autoimmune disease characterized by centralnervous system demyelination, multiple onset in young adults, the clinical symptomsand have recurrent disease, delayed healing characteristics, with disease progressionand a higher incidence of disability. The incidence of MS is the result of the combinedeffects of multiple factors, including T lymphocytes in MS pathology and biologicalprocesses of disease progression occurred in each play an important role. Lymphocytefunction-associated antigen-1(LFA-1) involved in the development anddifferentiation of immune cells involved in the immune response and immuneregulation, its role in helper T cell proliferation and differentiation attention. In thisstudy, the purpose is to observe the LFA-1gene knock case of experimentalautoimmune encephalomyelitis (EAE) mouse joint local draining lymph nodesaffected T cell activity and to detect CD4+T cells produce cytokines addition and toinvestigate the role of LFA-1regulatory T cell activity in multiple sclerosispathogenesis.Objective:To observe EAE incidence of LFA-1knockout mouse and to explore effects ofLFA-1gene on T cells during the onset of EAE.Methods:We induced EAE mouse model with MOG35-55peptide immunization inwild-type and LFA-1-knockout mice, observed EAE incidence in two groups of mice,detected the body weight, clinical symptoms and nerve damage case, and detected Tcell proliferation in draining lymph node (DLN) by BrdU assay, and cytokineproduction by CD4+T cells with flow cytometry.Results:After MOG induction, compared to wild type mice, EAE incidence of LFA-1knockout mice is reduced latency, the difference was statistically significant (P<0.01).And the incidence of mild, late onset neurological damage score lower in the earlystages, the difference between the two scores was significant (P<0.01). Except murineLFA-1gene compared to the knock body weight of wild-type mice occurs earlier fall time, the greater the decrease. Wild-type mice showed obvious spinal corddemyelination, while LFA-1-knockout mice had no significant pathological changes;Furthermore, in the day7, LFA-1-knockout mice showed the reduced DLNlymphocytes aggregation and MOG-specific T cell proliferation, and had lower ratioof IFN-γ and IL-17-sereted T cells compared to wild-type mice. But in day21, whilethe disease began to relieve, there are no obvious difference between LFA-1knockoutand wild-type mice.Conclusions:1. The incidence of EAE in LFA-1knockout mice was lower and the incubationperiod was longer and the clinical symptoms and nerve damage was milder than thewild-type mice.2. LFA-1knockout can influence the development of EAE by mechanisms ofreducing lymphocytes to lymph drainage, reducing T lymphocyte proliferation orstimulating Th1cells to secrete more IFN-γ and Th17cells to secrete more IL-17, etc.3. LFA-1may play a key role in the early stage of EAE, so that LFA-1may be animportant molecular target for treatment of EAE.