Lung-resident CD4⁺ T cells are sufficient for IL-4Rα-dependent recall immunity to Nippostrongylus brasiliensis infection

Research output: Contribution to journalArticle

Authors

  • S G Thawer
  • M Darby
  • J C Hoving
  • B Dewals
  • A J Cutler
  • D Lang
  • F Brombacher

Colleges, School and Institutes

External organisations

  • 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.
  • Department of Human Biology, Health Science Faculty, University of Cape Town, Cape Town, South Africa.

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.

Details

Original languageEnglish
Pages (from-to)239-248
Number of pages10
JournalMucosal immunology
Volume7
Issue number2
Early online date19 Jun 2013
Publication statusPublished - Mar 2014

Keywords

  • Animals, CD4-Positive T-Lymphocytes, Cell Movement, Disease Models, Animal, Gene Expression, Immunologic Memory, Interleukin-4 Receptor alpha Subunit, Lung, Lymph Nodes, Mice, Mice, Knockout, Nippostrongylus, Strongylida Infections, Journal Article, Research Support, Non-U.S. Gov't, CD4-positive T cells, Immunological memory, Parasite host response, Parasitic infection