CD4+CD25int T cells in inflammatory diseases refractory to treatment with glucocorticoids

Lee, R. W. J., Creed, T. J., Schewitz, L. P., Newcomb, P. V., Nicholson, L. B., Dick, A. D. and Dayan, Colin Mark ORCID: https://orcid.org/0000-0002-6557-3462 2007. CD4+CD25int T cells in inflammatory diseases refractory to treatment with glucocorticoids. The Journal of Immunology 179 (11) , pp. 7941-7948. 10.4049/jimmunol.179.11.7941

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Abstract

Up to 30% of patients with autoimmune, allergic, and lymphoproliferative diseases are refractory to glucocorticoid therapy. The present study was undertaken to investigate whether such steroid resistance (SR) is limited to a subpopulation of CD4+ T cells and, as IL-2 is a putative driver of SR, whether T cell SR is associated with CD25 expression. We show that SR patients have a characteristic subgroup of activated CD4+ T cells that continue to proliferate despite exposure to high-dose Dexamethasone (Dex), demonstrate that CD4+CD25− cells are exquisitely sensitive to Dex whereas CD4+CD25int cells are highly SR, and further find that the combination of an anti-CD25 mAb with Dex enhances suppression of T cell proliferation compared with each agent alone. We therefore conclude that SR is not a general property of all lymphocytes but resides in T cell subpopulations, which are prevalent in SR patients and express intermediary levels of CD25. As a result, we propose a new paradigm for SR disease in which glucocorticoid therapy positively selects SR cells, generating a population of drug-resistant lymphocytes that perpetuate on-going inflammation.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine Research Institutes & Centres > Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General)
Publisher:	American Association of Immunologists
ISSN:	0022-1767
Last Modified:	27 Oct 2022 08:54
URI:	https://orca.cardiff.ac.uk/id/eprint/63710

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