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IL‐4δ2, a natural splice variant of IL‐4, is a mediator of T cell recruitment
Author(s) -
Luzina Irina G.,
Lockatell Virginia,
Highsmith Kendrick,
Nacu Natalia,
Choi Jung,
Papadimitriou John C.,
Atamas Sergei P.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.664.11
Subject(s) - immunology , in vivo , cytokine , cd8 , t cell , microbiology and biotechnology , biology , il 2 receptor , bronchoalveolar lavage , interleukin , medicine , lung , immune system
We previously described a natural splice variant of IL‐4 that lacks exon 2, and reported that recombinant IL‐4δ2 antagonizes functional effects of IL‐4 on cultured T and B lymphocytes and monocytes. Changes in the absolute and relative expression levels of IL‐4 and IL‐4δ2 have been reported in the lungs of patients with asthma, tuberculosis, and HIV infection. Functional effects of IL‐4δ2 in vivo have not been characterized. Adenoviral gene delivery of IL‐4 or IL‐4δ2 to mouse lungs in vivo in comparison with AdV‐NULL infections was utilized. Overexpression of IL‐4 or IL‐4δ2 was confirmed by ELISA and LC/MS. Delivery of either IL‐4 or IL‐4δ2 caused profound peribronchial and perivascular infiltration of mostly T cell, equally CD4+ and CD8+, with some granulocytes, macrophages, and plasma cells. In the bronchoalveolar lavage cells, the relative contribution of lymphocytes changed from normal 1.7±1.2% to 33±8% in IL‐4‐expressing and 53±6% in IL‐4δ2‐expressing mice. Less than 1% of the infiltrating CD8+ cells but 17±3% of CD4+ cells and were also CD25+. These changes peaked at 7–14 days following the infections, and declined by 21–28 days. The implication based on experiments in cell culture that IL‐4δ2 is simply a passive inhibitor of IL‐4 effects is likely incorrect. The splice variant IL‐4δ2 is an active cytokine mediating pulmonary infiltration of mostly T cells in vivo. Support: R01HL074067, VA Merit (SPA).