IL-4-dependent Th2 collateral priming to inhaled antigens independent of Toll-like receptor 4 and myeloid differentiation factor 88.
Allergic asthma is an inflammatory lung disease thought to be initiated and directed by type 2 helper T cells responding to environmental Ags. The mechanisms by which allergens induce Th2-adaptive immune responses are not well understood, although it is now clear that innate immune signals are required to promote DC activation and Th2 sensitization to inhaled proteins. However, the effect of ongoing Th2 inflammation, as seen in chronic asthma, on naive lymphocyte activation has not been explored. It has been noted that patients with atopic disorders demonstrate an increased risk of developing sensitivities to new allergens. This suggests that signals from an adaptive immune response may facilitate sensitization to new Ags. We used a Th2-adoptive transfer murine model of asthma to identify a novel mechanism, termed "collateral priming," in which naive CD4(+) T cells are activated by adaptive rather than innate immune signals. Th2 priming to newly encountered Ags was dependent on the production of IL-4 by the transferred Th2 population but was independent of Toll-like receptor 4 signaling and the myeloid differentiation factor 88 Toll-like receptor signaling pathway. These results identify a novel mechanism of T cell priming in which an Ag-specific adaptive immune response initiates distinct Ag-specific T cell responses in the absence of classical innate immune system triggering signals.
Eisenbarth
Stephanie C
SC
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA. stephanie.eisenbarth@yale.edu
Zhadkevich
Alex
A
Ranney
Patricia
P
Herrick
Christina A
CA
Bottomly
Kim
K
D048868:Adaptor Proteins, Signal Transducing; D000280:Administration, Inhalation; D019264:Adoptive Transfer; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D000943:Antigens, Differentiation / Q000235:genetics / Q000502:physiology*; D001249:Asthma / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D004527:Egg Proteins / Q000008:administration & dosage / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015847:Interleukin-4 / Q000172:deficiency / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000637:transplantation; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D000485:Allergens; D000941:Antigens; D000943:Antigens, Differentiation; D004527:Egg Proteins; D018984:Epitopes, T-Lymphocyte; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C110366:OVA-8; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors; D015847:Interleukin-4; D012710:Serum Albumin, Bovine; D010047:Ovalbumin