Interleukin-4-promoted T helper 2 responses enhance Nippostrongylus brasiliensis-induced pulmonary pathology.
The role of CD4(+) T-cell interleukin-4 (IL-4) receptor alpha (IL-4Ralpha) expression in T helper 2 (TH2) immune responses has not been defined. To examine this role, we infected CD4(+) T-cell IL-4Ralpha knockout (KO) mice with the parasitic nematode Nippostrongylus brasiliensis, which induces strong host TH2 responses. Although N. brasiliensis expulsion was not affected in CD4(+) T-cell IL-4Ralpha KO mice, the associated lung pathology was reduced. Infected CD4(+) T-cell IL-4Ralpha KO mice showed abrogation of airway mucus production. Furthermore, CD4(+) T-cell IL-4Ralpha KO mouse lungs contained reduced numbers of lymphocytes and eosinophils. Restimulation of pulmonary region-associated T-cell populations showed that TH2 cytokine responses were disrupted. Secretion of IL-4, but not secretion of IL-13 or IL-5, from mediastinal lymph node CD4(+) T cells was reduced in infected CD4(+) T-cell IL-4Ralpha KO mice. Restimulation of tissue-derived CD4(+) T cells resulted in equivalent levels of IL-4 and IL-13 on day 7 postinfection (p.i.) in control and CD4(+) T-cell IL-4Ralpha KO mice. By day 10 p.i. the TH2 cytokine levels had significantly declined in CD4(+) T-cell IL-4Ralpha KO mice. Restimulation with N. brasiliensis antigen of total lung cell populations and populations with CD4(+) T cells depleted showed that CD4(+) T cells were a key TH2 cytokine source. These data demonstrated that CD4(+) T-cell IL-4 responsiveness facilitates eosinophil and lymphocyte recruitment, lymphocyte localization, and TH2 cytokine production in the allergic pathology associated with N. brasiliensis infections.
Mearns
Helen
H
International Centre for Genetic Engineering and Biotechnology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Horsnell
William G C
WG
Hoving
J Claire
JC
Dewals
Benjamin
B
Cutler
Antony J
AJ
Kirstein
Frank
F
Myburgh
Elmarie
E
Arendse
Berenice
B
Brombacher
Frank
F
D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007150:Immunohistochemistry; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D009559:Nippostrongylus / Q000276:immunology; D017206:Strongylida Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; D015847:Interleukin-4