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CD4 + T cells contribute to chronic hypoxia‐induced pulmonary hypertension (1090.5)
Author(s) -
Maston Levi,
Can Judy,
Resta Thomas,
González Bosc Laura
Publication year - 2014
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.28.1_supplement.1090.5
Subject(s) - recombination activating gene , adoptive cell transfer , immune system , pulmonary hypertension , hypoxia (environmental) , lymph , medicine , inflammation , microbiology and biotechnology , chemistry , endocrinology , immunology , t cell , biology , pathology , oxygen , biochemistry , organic chemistry , recombination , gene
We have previously demonstrated that adaptive immune cells contribute to chronic hypoxia (CH)‐induced pulmonary hypertension (PH). Within the adaptive immune system, CD4 + T cells are required for initiating and maintaining inflammation, suggesting these cells could play an important role in the pathology of hypoxic PH. Therefore, we hypothesized that CD4 + T cells contribute to CH‐induced PH. To test this hypothesis, we isolated CD4 + T cells from lymph nodes of male C57BL/6 wild‐type (WT) mice by negative selection or B cells from spleens of T cell receptor knockout (KO) mice lacking T cells. We then adoptively transferred B cells and CD4 + T cells separately into RAG1 KO mice, which lack mature T and B cells. WT mice and adoptively transferred and sham‐treated RAG1 KO mice were exposed to normoxia or CH (P B =380 mmHg) for 3 weeks, at which point peak right ventricular systolic pressure (RVSP) was measured. As previously observed, sham‐treated RAG1 KO mice were protected from the development of CH‐induced PH as indicated by significantly lower RVSP compared to CH WT mice (p<0.05). In support of our hypothesis, adoptive transfer of CD4 + T cells, but not B cells, to CH RAG1 KO mice restored the PH phenotype to the level of CH WT mice. We conclude that CD4 + T cells are sufficient to drive CH‐induced PH. Grant Funding Source : Supported by T32 HL07736, R01HL088151, R01 HL088192, R01 AI097202