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Basophils are recruited to inflamed lungs and exacerbate memory T h2 responses in mice and humans
Author(s) -
Wakahara K.,
Van V. Q.,
Baba N.,
Bégin P.,
Rubio M.,
Delespesse G.,
Sarfati M.
Publication year - 2013
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12072
Subject(s) - immunology , adoptive cell transfer , foxp3 , bronchoalveolar lavage , ovalbumin , t cell , cytokine , flow cytometry , allergic inflammation , biology , inflammation , medicine , lung , immune system
Background Although the contribution of basophils as inducers or amplifiers of T h2 responses is still debated, prolonged basophil/ CD 4 T cell interactions were observed in lungs but not lymph nodes ( LN s) of parasite‐infected mice. However, the impact of basophils on the function of tissue CD 4 effector T cells remains unknown. Methods Basophils were purified from the lungs of ovalbumin ( OVA )‐sensitized and OVA ‐challenged ( OVA ‐immunized) mice or human peripheral blood for in vivo and in vitro functional studies. Pulmonary basophils were adoptively transferred to OVA ‐sensitized hosts to assess airway inflammation in bronchoalveolar lavage fluid ( BALF ) and T h2 responses in lung explants and draining LN s. Basophils were co‐cultured with effector T cells or A g‐specific naïve T cells alone or in combination with dendritic cells ( DC s); IL ‐4 production was determined by flow cytometry and ELISA . Results Basophils accumulated in lungs of OVA ‐immunized mice. Adoptive transfer of basophils to OVA ‐sensitized hosts enhanced lung IL ‐4 and IL ‐13 release while co‐administration of OVA further aggravated airway inflammation and T h2 responses in LN s. Mechanistic in vitro studies revealed that pulmonary basophils interacted with lung CD 4 effectors, in the absence of DC s, to increase T cell survival and T h2 cytokine expression at the single cell level but amplified OVA ‐loaded DC ‐driven T h2 differentiation. Finally, human basophils augmented in vitro IL ‐4 expression in effector memory CD 4 T cells that include CRTH 2 + cells through IL ‐4 and TCR ‐independent pathways. Conclusions Basophils may worsen T h2 inflammatory disorders through direct interactions with pathogenic CD 4 T cells as well as by enhancing DC ‐induced T h2 cell development.