title: Lung-resident CD4⁺ T cells are sufficient for IL-4Rα-dependent recall immunity to Nippostrongylus brasiliensis infection.
abstract: Immunity to Nippostrongylus brasiliensis reinfection requires pulmonary CD4⁺ T-cell responses. We examined whether secondary lymphoid recruited or pre-existing lung CD4⁺ T-cell populations coordinated this immunity. To do this, we blocked T-cell egress from lymph nodes using Fingolimod (FTY720). This impaired host ability to resolve a primary infection but did not change effectiveness of recall immunity. Associated with this effective recall immunity was the expansion and T helper type 2 polarization of a pre-existing pulmonary CD4⁺ T-cell population. LTβR-Ig (lymphotoxin beta-receptor fusion protein)-mediated disruption of stromal cell organization of immune cells did not disrupt this recall immunity, suggesting that protection was mediated by a pulmonary interstitial residing CD4⁺ T-cell population. Adoptive transfer of N. brasiliensis-experienced pulmonary CD4⁺ T cells from FTY720-treated wild-type or T-cell interleukin (IL)-4Rα-deficient mice demonstrated protection to be IL-4Rα dependent. These results show that pre-existing CD4⁺ T cells can drive effective recall immunity to N. brasiliensis infection independently of T-cell recruitment from secondary lymphoid organs.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology/Institute of Infectious Diseases and Molecular Medicine, Health Science Faculty, University of Cape Town, Cape Town, South Africa.
authors.forename: S G
authors.initials: SG
authors.lastname: Thawer
authors.affiliation: International Centre for Genetic Engineering and Biotechnology/Institute of Infectious Diseases and Molecular Medicine, Health Science Faculty, University of Cape Town, Cape Town, South Africa.
authors.forename: W G C
authors.initials: WG
authors.lastname: Horsnell
authors.affiliation: International Centre for Genetic Engineering and Biotechnology/Institute of Infectious Diseases and Molecular Medicine, Health Science Faculty, University of Cape Town, Cape Town, South Africa.
authors.forename: M
authors.initials: M
authors.lastname: Darby
authors.affiliation: International Centre for Genetic Engineering and Biotechnology/Institute of Infectious Diseases and Molecular Medicine, Health Science Faculty, University of Cape Town, Cape Town, South Africa.
authors.forename: J C
authors.initials: JC
authors.lastname: Hoving
authors.affiliation: International Centre for Genetic Engineering and Biotechnology/Institute of Infectious Diseases and Molecular Medicine, Health Science Faculty, University of Cape Town, Cape Town, South Africa.
authors.forename: B
authors.initials: B
authors.lastname: Dewals
authors.affiliation: International Centre for Genetic Engineering and Biotechnology/Institute of Infectious Diseases and Molecular Medicine, Health Science Faculty, University of Cape Town, Cape Town, South Africa.
authors.forename: A J
authors.initials: AJ
authors.lastname: Cutler
authors.affiliation: Department of Human Biology, Health Science Faculty, University of Cape Town, Cape Town, South Africa.
authors.forename: D
authors.initials: D
authors.lastname: Lang
authors.affiliation: International Centre for Genetic Engineering and Biotechnology/Institute of Infectious Diseases and Molecular Medicine, Health Science Faculty, University of Cape Town, Cape Town, South Africa.
authors.forename: F
authors.initials: F
authors.lastname: Brombacher
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D015870:Gene Expression; D007156:Immunologic Memory; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009559:Nippostrongylus / Q000276:immunology*; D017206:Strongylida Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology
chemical_list: D053662:Interleukin-4 Receptor alpha Subunit