IL-5 promotes induction of antigen-specific CD4+CD25+ T regulatory cells that suppress autoimmunity.
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.
Immune Tolerance Laboratory, Faculty of Medicine, University of New South Wales, Sydney, Australia.
Giang T
GT
Tran
Suzanne J
SJ
Hodgkinson
Nicole M
NM
Carter
Nirupama D
ND
Verma
Karren M
KM
Plain
Rochelle
R
Boyd
Catherine M
CM
Robinson
Masaru
M
Nomura
Murray
M
Killingsworth
Bruce M
BM
Hall
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D015551:Autoimmunity / Q000187:drug effects* / Q000276:immunology; D015704:CD4 Antigens / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004353:Drug Evaluation, Preclinical; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D015848:Interleukin-5 / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000494:pharmacology; D037182:T-Cell Antigen Receptor Specificity / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D015848:Interleukin-5; D011994:Recombinant Proteins