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

Mucosal Immunol. 2014 Mar;7(2):239-48. doi: 10.1038/mi.2013.40. Epub 2013 Jun 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Disease Models, Animal
  • Gene Expression
  • Immunologic Memory*
  • Interleukin-4 Receptor alpha Subunit / genetics
  • Interleukin-4 Receptor alpha Subunit / metabolism*
  • Lung / immunology*
  • Lung / metabolism*
  • Lung / parasitology
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Mice
  • Mice, Knockout
  • Nippostrongylus / immunology*
  • Strongylida Infections / genetics
  • Strongylida Infections / immunology*
  • Strongylida Infections / metabolism*
  • Strongylida Infections / parasitology

Substances

  • Interleukin-4 Receptor alpha Subunit