PD‐1 expression is upregulated on adapted T cells in experimental autoimmune encephalomyelitis but is not required to maintain a hyporesponsive state. Issue 1 (7th December 2018)

• Record Type: Journal Article
• Authors: Mair, Iris; Besusso, Dario; Saul, Louise; Patel, Sarju D.; Ravindran, Rahul; McPherson, Rhoanne C.; Leech, Melanie D.; O'Connor, Richard A.; Anderton, Stephen M.; Mellanby, Richard J.
• Is Part Of: European journal of immunology. Volume 49:Issue 1(2019)
• Page Start: 112
• Page End: 120
• Publication Date: 2018-12-07
• Subjects: Adaptation -- Autoimmunity -- Experimental autoimmune encephalomyelitis -- PD‐1 -- T cell; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201847868
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: T cell adaptation is an important peripheral tolerogenic process which ensures that the T cell population can respond effectively to pathogens but remains tolerant to self‐antigens. We probed the mechanisms of T cell adaptation using an experimental autoimmune encephalomyelitis (EAE) model in which the fate of autopathogenic T cells could be followed. We demonstrated that immunisation with a high dose of myelin basic protein (MBP) peptide and complete Freund's adjuvant failed to effectively initiate EAE, in contrast to low dose MBP peptide immunisation which readily induced disease. The proportion of autopathogenic CD4 + T cells in the central nervous system (CNS) of mice immunised with a high dose of MBP peptide was not significantly different to mice immunised with a low dose. However, autopathogenic T cells in mice immunised with high dose MBP peptide had an unresponsive phenotype in ex vivo recall assays. Importantly, whilst expression of PD‐1 was increased on adapted CD4 + T cells within the CNS, loss of PD‐1 function did not prevent the development of the unresponsive state. The lack of a role for PD‐1 in the acquisition of the adapted state stands in striking contrast to the reported functional importance of PD‐1 in T cell unresponsiveness in other disease models. Abstract : Immunisation of host mice seeded with MBP‐reactive CD4 + T cells with a high dose of agonist peptide results in a lack of development of experimental autoimmune encephalomyelitis due to T cell adaptation. In contrast to other reported hyporesponsive T cell states, the adapted phenotype in this autoimmune disease model is not PD‐1 dependent.