title: IL-10+ CTLA-4+ Th2 inhibitory cells form in a Foxp3-independent, IL-2-dependent manner from Th2 effectors during chronic inflammation.
abstract: Activated Th cells influence other T cells via positive feedback circuits that expand and polarize particular types of response, but little is known about how they may also initiate negative feedback against immunopathological reactions. In this study, we demonstrate the emergence, during chronic inflammation, of GATA-3(+) Th2 inhibitory (Th2i) cells that express high levels of inhibitory proteins including IL-10, CTLA-4, and granzyme B, but do so independently of Foxp3. Whereas other Th2 effectors promote proliferation and IL-4 production by naive T cells, Th2i cells suppress proliferation and IL-4 production. We show that Th2i cells develop directly from Th2 effectors, in a manner that can be promoted by effector cytokines including IL-2, IL-10, and IL-21 ex vivo and that requires T cell activation through CD28, Card11, and IL-2 in vivo. Formation of Th2i cells may act as an inbuilt activation-induced feedback inhibition mechanism against excessive or chronic Th2 responses.
authors.affiliation: Department of Immunology, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory 0200, Australia.
authors.forename: John A
authors.initials: JA
authors.lastname: Altin
authors.forename: Chris C
authors.initials: CC
authors.lastname: Goodnow
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Cook
mesh_terms: D000818:Animals; D060908:CTLA-4 Antigen / Q000096:biosynthesis* / Q000172:deficiency; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D051858:Forkhead Transcription Factors / Q000172:deficiency / Q000502:physiology; D053804:Granzymes / Q000096:biosynthesis; D007108:Immune Tolerance / Q000235:genetics; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D016753:Interleukin-10 / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C556062:IL10 protein, mouse; D018836:Inflammation Mediators; D007376:Interleukin-2; D016753:Interleukin-10; D053804:Granzymes; C509214:Gzmb protein, mouse