IL-5 promotes induction of antigen-specific CD4(+)CD25(+) T regulatory cells that suppress autoimmunity

Giang T Tran, Suzanne J Hodgkinson, Nicole M Carter, Nirupama Darshan Verma, Karren Michelle Plain, Rochelle Boyd, Catherine M Robinson, Masaru Nomura, Murray Killingsworth, Bruce M Hall

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49 Citations (Scopus)

Abstract

Immune responses to foreign and self-Ags can be controlled by regulatory T cells (Tregs) expressing CD4 and IL-2Rα chain (CD25). Defects in Tregs lead to autoimmunity, whereas induction of Ag-specific CD4+CD25+ Tregs restores tolerance. Ag-specific CD4+CD25+ FOXP3+Tregs activated by the T helper type 2 (Th2) cytokine, IL-4, and specific alloantigen promote allograft tolerance. These Tregs expressed the specific IL-5Rα and in the presence of IL-5 proliferate to specific but not third-party Ag. These findings suggest that recombinant IL-5 (rIL-5) therapy may promote Ag-specific Tregs to mediate tolerance. This study showed normal CD4+CD25+ Tregs cultured with IL-4 and an autoantigen expressed Il-5rα. Treatment of experimental autoimmune neuritis with rIL-5 markedly reduced clinical paralysis, weight loss, demyelination, and infiltration of CD4+ (Th1 and Th17) CD8+ T cells and macrophages in nerves. Clinical improvement was associated with expansion of CD4+CD25+FOXP3+ Tregs that expressed Il-5rα and proliferated only to specific autoantigen that was enhanced by rIL-5. Depletion of CD25+ Tregs or blocking of IL-4 abolished the benefits of rIL-5. Thus, rIL-5 promoted Ag-specific Tregs, activated by autoantigen and IL-4, to control autoimmunity. These findings may explain how Th2 responses, especially to parasitic infestation, induce immune tolerance. rIL-5 therapy may be able to induce Ag-specific tolerance in autoimmunity.

Original languageEnglish
Pages (from-to)4441-50
Number of pages10
JournalBlood
Volume119
Issue number19
DOIs
Publication statusPublished - 10 May 2012
Externally publishedYes

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    Tran, G. T., Hodgkinson, S. J., Carter, N. M., Verma, N. D., Plain, K. M., Boyd, R., ... Hall, B. M. (2012). IL-5 promotes induction of antigen-specific CD4(+)CD25(+) T regulatory cells that suppress autoimmunity. Blood, 119(19), 4441-50. https://doi.org/10.1182/blood-2011-12-396101