title: The Contained Self-Reactive Peripheral T Cell Repertoire: Size, Diversity, and Cellular Composition.
abstract: Individual self-reactive T cells have been discovered in both humans and mice. It is difficult to assess the entire contained self-reactive peripheral T cell repertoire in healthy individuals because regulatory T cells (Tregs) can render these cells anergic and, therefore, functionally indistinguishable. We addressed this issue by removing regulatory T cells, thereby allowing us to characterize the exposed self-reactive T cells. This resulted in activation of approximately 4% of both CD4(+) and CD8(+) T cells. Activation and division of these cells was not a bystander product of Ag-independent signals but required TCR stimulation. Analysis of TCR sequences showed that these responding cells were polyclonal and encompassed a broad range of structural TCR diversity. Adoptive transfer of naive and effector/memory T cell populations showed that even the naive T cell pool contained self-reactive T cell precursors. In addition, transfer of mature thymocytes showed that this response was an intrinsic T cell property rather than a peripheral adaptation. Finally, we found that the unexpectedly strong contribution of the naive CD5(low) T cell pool showed that the overall self-reactive response has not only a diverse polyclonal TCR repertoire, but also comprises a broad range of affinities for self.
authors.affiliation: Immune Tolerance, Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany; and.
authors.forename: David M
authors.initials: DM
authors.lastname: Richards
authors.affiliation: Division of Translational Oncology, German Cancer Research Center and National Center for Tumor Diseases, 69120 Heidelberg, Germany.
authors.forename: Eliana
authors.initials: E
authors.lastname: Ruggiero
authors.affiliation: Immune Tolerance, Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany; and.
authors.forename: Ann-Cathrin
authors.initials: AC
authors.lastname: Hofer
authors.affiliation: Immune Tolerance, Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany; and.
authors.forename: Julian P
authors.initials: JP
authors.lastname: Sefrin
authors.affiliation: Division of Translational Oncology, German Cancer Research Center and National Center for Tumor Diseases, 69120 Heidelberg, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Division of Translational Oncology, German Cancer Research Center and National Center for Tumor Diseases, 69120 Heidelberg, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: von Kalle
authors.affiliation: Immune Tolerance, Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany; and m.feuerer@dkfz-heidelberg.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Feuerer
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D054504:Precursor Cells, T-Lymphoid / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D011948:Receptors, Antigen, T-Cell