CD4(+) T cells prevent spontaneous experimental autoimmune encephalomyelitis in anti-myelin basic protein T cell receptor transgenic mice.
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, gamma/delta T cells, or alpha/beta T cells indicated that alpha/beta 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.
Van de Keere
F
F
Howard Hughes Medical Institute, the Center for Cancer Research, and the Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Tonegawa
S
S
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology; D005434:Flow Cytometry; D051379:Mice; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology*; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D004676:Myelin Basic Protein; D011948:Receptors, Antigen, T-Cell