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Role of CD47 in CD4+ T cell Proliferation after TCR Stimulation
Author(s) -
Azcutia Veronica,
Newton Gail,
Bassil Ribal,
Khoury Samia,
Elyaman Wassim,
Luscinskas Francis
Publication year - 2015
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.29.1_supplement.285.3
Subject(s) - t cell , il 2 receptor , cd28 , cd47 , naive t cell , microbiology and biotechnology , t cell receptor , biology , cell growth , interleukin 21 , immune system , chemistry , immunology , biochemistry
CD47 is involved in adaptive immune responses and leukocyte homeostasis. Han and colleagues (JEM 209:1325, 2012) have reported that CD47‐/‐ mice are protected from (MOG)35‐55 peptide induced experimental autoimmune encephalomyelitis (EAE), but not from passive EAE, suggesting a defect in the immune cell compartment. They concluded a defect in T cell proliferation due to failed T cell activation. We also observed CD47‐/‐ are not susceptible to MOG‐induced EAE, and have reduced CD4 T cell proliferation after MOG immunization in vivo and MOG‐dependent recall proliferation assay in vitro. However, in our hands CD47‐/‐ T cells from MOG‐immunized mice express identical levels of surface activation markers (CD69, CD44, IL2R, PD‐1) vs WT cells, and similar levels of intracellular cytokine production. CD47‐/‐ T cells also have defective Ag independent expansion after TCR stimulation, even though proximal signaling events (p‐Lck, p‐ZAP‐70, p‐ERK1/2) are identical to WT cells using FACS and CyTOF mass spectrometry. Intriguingly, kinetics of CD47‐/‐ T cell proliferation and cell cycle analyzed by CSFE dye dilution and by DNA staining respectively, show a comparable proliferative response to WT cells in the first 48h, but fail to proliferate beyond day 3. Accordingly, CD47‐/‐ CD4 T cells show a 2.3 fold increase in Annexin‐V staining and a 40% reduced [H 3 ]thymidine incorporation vs WT. In summary, CD47‐/‐ CD4 T cells become activated by MOG or TCR stimulation, but fail to maintain clonal expansion. We suggest this is due to defects in cell cycle machinery and/or increased cell apoptosis. This work was supported by NIH P01HL03628 and AHA 11POST7730055.