T Cell Repertoire in Lupus: Autoreactive T Cells in Central and Peripheral Selection
Main Article Content
Abstract
Systemic lupus erythematosus (SLE) is an immune disorder characterized by the presence of T and B cells which drive a pathogenic autoimmune response. Autoreactive T effector cells naturally arise during the process of development in the thymus, but most are removed by several self-tolerance mechanisms. Self-antigen recognizing T cells emigrating from the thymus are normally prevented from causing cellular or tissue damage by peripheral tolerance mechanisms. While we understand much about how self-antigens are presented to T cells and the mechanisms to remove those T cells or convert them into regulatory T cells in thymus and peripheral lymphoid organs, we understand much less about the derivation of potentially pathogenic self-reactive T cells in autoimmune disease. It is not clear whether individuals with autoreactive T cell activation have an altered T cell receptor repertoire of naïve T cells that have matured to immunocompetence as effector cells or whether the pathogenic process involves altered activation of immunocompetent T cells in the periphery. There is increasing evidence that the autoantibodies that characterize SLE result from an interaction of B cells with self-reactive T cells. Here we summarize the evidence for autoreactive T cells in both lupus mouse models and in patients with SLE and discuss the evidence for either altered T cell selection or altered T cell activation in SLE, which has implications for both pathogenesis and treatment
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KIM, Sun Jung; DIAMOND, Betty.
T Cell Repertoire in Lupus: Autoreactive T Cells in Central and Peripheral Selection.
Medical Research Archives, [S.l.], v. 12, n. 8, aug. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/5637>. Date accessed: 06 sep. 2024.
doi: https://doi.org/10.18103/mra.v12i8.5637.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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5. Malkiel S, Jeganathan V, Wolfson S, et al. Checkpoints for Autoreactive B Cells in the Peripheral Blood of Lupus Patients Assessed by Flow Cytometry. Arthritis Rheumatol. Sep 2016;68(9):2210-20. doi:10.1002/art.39710
6. Crow MK, DelGiudice-Asch G, Zehetbauer JB, et al. Autoantigen-specific T cell proliferation induced by the ribosomal P2 protein in patients with systemic lupus erythematosus. J Clin Invest. Jul 1994;94(1):345-52. doi:10.1172/JCI117328
7. Klein L, Hinterberger M, Wirnsberger G, Kyewski B. Antigen presentation in the thymus for positive selection and central tolerance induction. Nat Rev Immunol. Dec 2009;9(12):833-44. doi:10.1038/nri2669
8. Kyewski B, Klein L. A central role for central tolerance. Annu Rev Immunol. 2006;24:571-606. doi:10.1146/annurev.immunol.23.021704.115601
9. Lee HM, Bautista JL, Scott-Browne J, Mohan JF, Hsieh CS. A broad range of self-reactivity drives thymic regulatory T cell selection to limit responses to self. Immunity. Sep 21 2012;37(3):475-86. doi:10.1016/j.immuni.2012.07.009
10. Nedjic J, Aichinger M, Emmerich J, Mizushima N, Klein L. Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance. Nature. Sep 18 2008;455(7211):396-400. doi:10.1038/nature07208
11. Florea BI, Verdoes M, Li N, et al. Activity-based profiling reveals reactivity of the murine thymoproteasome-specific subunit beta5t. Chem Biol. Aug 27 2010;17(8):795-801. doi:10.1016/j.chembiol.2010.05.027
12. Nakagawa T, Roth W, Wong P, et al. Cathepsin L: critical role in Ii degradation and CD4 T cell selection in the thymus. Science. Apr 17 1998;280(5362):450-3. doi:10.1126/science.280.5362.450
13. Gommeaux J, Gregoire C, Nguessan P, et al. Thymus-specific serine protease regulates positive selection of a subset of CD4+ thymocytes. Eur J Immunol. Apr 2009;39(4):956-64. doi:10.1002/eji.200839175
14. McCaughtry TM, Baldwin TA, Wilken MS, Hogquist KA. Clonal deletion of thymocytes can occur in the cortex with no involvement of the medulla. J Exp Med. Oct 27 2008;205(11):2575-84. doi:10.1084/jem.20080866
15. Melichar HJ, Ross JO, Herzmark P, Hogquist KA, Robey EA. Distinct temporal patterns of T cell receptor signaling during positive versus negative selection in situ. Sci Signal. Oct 15 2013;6(297):ra92. doi:10.1126/scisignal.2004400
16. Takaba H, Morishita Y, Tomofuji Y, et al. Fezf2 Orchestrates a Thymic Program of Self-Antigen Expression for Immune Tolerance. Cell. Nov 5 2015;163(4):975-87. doi:10.1016/j.cell.2015.10.013
17. Hubert FX, Kinkel SA, Davey GM, et al. Aire regulates the transfer of antigen from mTECs to dendritic cells for induction of thymic tolerance. Blood. Sep 1 2011;118(9):2462-72. doi:10.1182/blood-2010-06-286393
18. Yu W, Jiang N, Ebert PJ, et al. Clonal Deletion Prunes but Does Not Eliminate Self-Specific alphabeta CD8(+) T Lymphocytes. Immunity. May 19 2015;42(5):929-41. doi:10.1016/j.immuni.2015.05.001
19. La Gruta NL, Rothwell WT, Cukalac T, et al. Primary CTL response magnitude in mice is determined by the extent of naive T cell recruitment and subsequent clonal expansion. J Clin Invest. Jun 2010;120(6):1885-94. doi:10.1172/JCI41538
20. La Gruta NL, Thomas PG, Webb AI, et al. Epitope-specific TCRbeta repertoire diversity imparts no functional advantage on the CD8+ T cell response to cognate viral peptides. Proc Natl Acad Sci U S A. Feb 12 2008;105(6):2034-9. doi:10.1073/pnas.0711682102
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