Chronic Modulation of the TCR Repertoire in the Lymphoid Periphery

• Published in: The Journal of immunology (1950) Vol. 162; no. 6; pp. 3131 - 3140
• Main Authors: Blish, Catherine A, Gallay, Brian J, Turk, Gail L, Kline, Khristina M, Wheat, William, Fink, Pamela J
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15-03-1999
• Subjects: Aging - immunology; AIDS/HIV; Animals; Bone Marrow Cells - immunology; Bone Marrow Cells - metabolism; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - metabolism; Cell Differentiation - immunology; Clonal Deletion; Histocompatibility Antigens Class II - biosynthesis; Lymphoid Tissue - cytology; Lymphoid Tissue - immunology; Lymphoid Tissue - metabolism; Male; Mammary Tumor Virus, Mouse - immunology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Receptors, Antigen, T-Cell, alpha-beta - biosynthesis; Receptors, Antigen, T-Cell, alpha-beta - chemistry; Receptors, Antigen, T-Cell, alpha-beta - metabolism; Superantigens - immunology; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.162.6.3131

Using TCR V beta 5 transgenic mice as a model system, we demonstrate that the induction of peripheral tolerance can mold the TCR repertoire throughout adult life. In these mice, three distinct populations of peripheral T cells are affected by chronic selective events in the lymphoid periphery. First, CD4+V beta 5+ T cells are deleted in the lymphoid periphery by superantigens encoded by mouse mammary tumor viruses-8 and -9 in an MHC class II-dependent manner. Second, mature CD8+V beta 5+ T cells transit through a CD8lowV beta 5low deletional intermediate during tolerance induction by a process that depends upon neither mouse mammary tumor virus-encoded superantigens nor MHC class II expression. Third, a population of CD4-CD8-V beta 5+ T cells arises in the lymphoid periphery in an age-dependent manner. We analyzed the TCR V alpha repertoire of each of these cellular compartments in both V beta 5 transgenic and nontransgenic C57BL/6 mice as a function of age. This analysis revealed age-related changes in the expression of V alpha families among different cellular compartments, highlighting the dynamic state of the peripheral immune repertoire. Our work indicates that the chronic processes maintaining peripheral T cell tolerance can dramatically shape the available TCR repertoire.