Differences between two strains of myelin basic protein (MBP) TCR transgenic mice: implications for tolerance induction.
Experimental autoimmune encephalomyelitis (EAE) is mediated by CD4+ T cells which preferentially use the Vbeta8.2 TCR in response to myelin basic protein (MBP). Two strains of Tg mice (Valpha2.3/Vbeta8.2 and Valpha4/Vbeta8.2) have T cell receptors that recognize the NAc1-11 immunodominant epitope of MBP. We previously reported that oral administration of MBP protects both Valpha2.3/Vbeta8.2 and Valpha4/Vbeta8.2 mice from EAE; however, tolerance induction differs between strains and is dependent on the timing of oral antigen. Here we analyze the peripheral and gut-associated lymphoid tissue (GALT) environments of the two strains of Tg mice. Tg cells in the Peyer's patch (PP) but not the spleen of Valpha2.3/Vbeta8.2 mice demonstrate increased CD69 and decreased CD45RB relative to Valpha4/Vbeta8.2 mice. High levels of Th1 and Th2 cytokines, proliferative activity and CC chemokines (MCP-1) are observed in the periphery and GALT of Valpha2.3/Vbeta8.2 Tg mice. In contrast, more non-Tg CD4+ cells are seen in the PP of Valpha4/Vbeta8.2 mice. These studies suggest that activated Tg T cells and fewer potential regulatory cells in the PP of Valpha2.3/Vbeta8.2 Tg mice may influence oral tolerance.
Song
Fei
F
Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University College of Medicine and Public Health, Columbus 43210, USA.
Wardrop
Richard M
RM
Gienapp
Ingrid E
IE
Stuckman
Scott S
SS
Goverman
Joan
J
Whitacre
Caroline C
CC
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002469:Cell Separation; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D007108:Immune Tolerance / Q000235:genetics*; D016056:Immunodominant Epitopes / Q000008:administration & dosage / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology*; D010446:Peptide Fragments / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology*; D013045:Species Specificity; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D018932:Chemokine CCL2; D016207:Cytokines; D016056:Immunodominant Epitopes; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; C109168:T-cell receptor Vbeta 8.2