CD4 T cell tolerance to nuclear proteins induced by medullary thymic epithelium.
Thymic epithelium is involved in negative selection, but its precise role in selecting the CD4 T cell repertoire remains elusive. By using two transgenic mice, we have investigated how medullary thymic epithelium (mTE) and bone marrow (BM)-derived cells contribute to tolerance of CD4 T cells to nuclear beta-galactosidase (beta-gal). CD4 T cells were not tolerant when beta-gal was expressed in thymic BM-derived cells. In contrast, CD4 T cells of mice expressing beta-gal in mTE were tolerized. Tolerance resulted from presentation of endogenous beta-gal by mTE cells but not from cross-priming. mTE cells presented nuclear beta-gal to a Th clone in vitro, while thymic dendritic cells did not. The data indicate that mTE but not thymic BM-derived cells can use a MHC class II endogenous presentation pathway to induce tolerance to nuclear proteins.
Oukka
M
M
Institut National de la Santé et de la Recherche Médicale U 267, Villejuif, France.
Colucci-Guyon
E
E
Tran
P L
PL
Cohen-Tannoudji
M
M
Babinet
C
C
Lotteau
V
V
Kosmatopoulos
K
K
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004847:Epithelial Cells; D004848:Epithelium / Q000276:immunology; D018858:Germinal Center / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013950:Thymus Gland / Q000033:anatomy & histology / Q000276:immunology*; D001616:beta-Galactosidase / Q000235:genetics
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D001616:beta-Galactosidase