CD40-mediated activation of T cells accelerates, but is not required for, encephalitogenic potential of myelin basic protein-recognizing T cells in a model of progressive experimental autoimmune encephalomyelitis

2001 ◽  
Vol 31 (2) ◽  
pp. 527-538 ◽  
Author(s):  
Sara Abromson-Leeman ◽  
Emanual Maverakis ◽  
Roderick Bronson ◽  
Martin E. Dorf
Keyword(s):  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

scholarly journals CD4+ T Cells Prevent Spontaneous Experimental Autoimmune Encephalomyelitis in Anti–Myelin Basic Protein T Cell Receptor Transgenic Mice

1998 ◽  
Vol 188 (10) ◽  
pp. 1875-1882 ◽  
Author(s):  
Fabienne Van de Keere ◽  
Susumu Tonegawa
Keyword(s):  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Transgenic Mice ◽  
Myelin Basic Protein ◽  
Cd4 T Cells ◽  
Basic Protein ◽  
Regulatory Function ◽  
Autoimmune Encephalomyelitis ◽  
Rag 1 ◽  
Experimental Autoimmune

Autoimmune diseases result from a failure of tolerance. Although many self-reactive T cells are present in animals and humans, their activation appears to be prevented normally by regulatory T cells. In this study, we show that regulatory CD4+ T cells do protect mice against the spontaneous occurrence of experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis. Anti–myelin basic protein (MBP) TCR transgenic mice (T/R+) do not spontaneously develop EAE although many self-reactive T cells are present in their thymi and peripheral lymphoid organs. However, the disease develops in all crosses of T/R+ mice with recombination-activating gene (RAG)-1 knockout mice in which transgenic TCR-expressing cells are the only lymphocytes present (T/R− mice). In this study, crosses of T/R+ mice with mice deficient for B cells, CD8+ T cells, NK1.1 CD4+ T (NKT) cells, γ/δ T cells, or α/β T cells indicated that α/β CD4+ T cells were the only cell population capable of controlling the self-reactive T cells. To confirm the protective role of CD4+ T cells, we performed adoptive transfer experiments. CD4+ T cells purified from thymi or lymph nodes of normal mice prevented the occurrence of spontaneous EAE in T/R− mice. To achieve full protection, the cells had to be transferred before the recipient mice manifested any symptoms of the disease. Transfer of CD4+ T cells after the appearance of symptoms of EAE had no protective effect. These results indicate that at least some CD4+ T cells have a regulatory function that prevent the activation of self-reactive T cells.

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