Origin of regulatory T cells with known specificity for antigen.
T cell receptor agonists can induce the differentiation of regulatory T (T(R)) cells. We report here that the immunoglobulin kappa-controlled expression of an agonist in different cell types correlated with the phenotype of the generated T(R) cells. We found that aberrant expression on thymic stroma yielded predominantly CD4(+)CD25(+) T(R) cells, which--under physiological conditions--may be induced by ectopically expressed organ-specific antigens and thus prevent organ-specific autoimmunity. Expression of the agonist antigen by nonactivated hematopoietic cells produced mostly CD4(+)CD25(-) T(R) cells. This subset can be derived from mature monospecific T cells without "tutoring" by other T cells and can be generated in the absence of a functioning thymus. Suppression of CD4(+) T cell proliferative responses by both CD25(+) and CD25(-) subsets was interleukin 10 (IL-10) independent and was overcome by IL-2. These data suggest that distinct pathways can be exploited to interfere with unwanted immune responses.
Apostolou
Irina
I
Harvard Medical School, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
Sarukhan
Adelaida
A
Klein
Ludger
L
von Boehmer
Harald
H
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D006388:Hemagglutinins / Q000235:genetics / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008822:Mice, Transgenic; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D006388:Hemagglutinins; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2