Specificity requirements for selection and effector functions of CD25+4+ regulatory T cells in anti-myelin basic protein T cell receptor transgenic mice.
CD25(+)4(+) regulatory T cells (T(reg)) play an indispensable role in preventing autoimmunity. Little is known, however, about the antigen specificities required for their development and effector functions. Mice transgenic for an anti-myelin basic protein (MBP) T cell antigen receptor (TCR) spontaneously develop experimental autoimmune encephalomyelitis (EAE) when deficient for the RAG-1 gene (T/R(-)), whereas RAG-1-competent transgenic animals (T/R(+)) remain healthy, protected by CD4(+) T(reg)-expressing endogenous TCRs. We have now investigated the role and specificity of CD25(+)4(+) T(reg) in this system. The results show that T/R(+) animals contain MBP-specific suppressive CD25(+)4(+) cells, whereas T/R(-) do not. Adoptive transfer of CD25(+)4(+) cells from nontransgenic or T/R(+) donors into T/R(-) mice prevented the development of EAE. Surprisingly, transfer of nontransgenic CD25(+)4(+) cells purified from T/R(+) donors conferred only a limited protection, possibly because of their restricted repertoire diversity that we demonstrate here. Absence of transgenic CD25(+)4(+) cells in animals deficient for endogenous TCRalpha chains and analyses of endogenous TCR gene expression in subsets of CD4(+) cells from T/R(+) mice demonstrate that development of transgenic MBP-specific CD25(+)4(+) T(reg) depends on the coexpression of endogenous TCRalpha chains. Taken together, these results indicate that specificity to MBP is required for effector functions but is not sufficient for thymic selection/commitment of CD25(+)4(+) T(reg) preventing EAE.
Hori
Shohei
S
Instituto Gulbenkian de Ciência, Apartado 14, 2781-901 Oeiras, Portugal.
Haury
Matthias
M
Coutinho
António
A
Demengeot
Jocelyne
J
D000818:Animals; D000918:Antibody Specificity; D015704:CD4 Antigens / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D015704:CD4 Antigens; D018398:Homeodomain Proteins; D004676:Myelin Basic Protein; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; C064658:RAG-1 protein