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Selenoprotein deficiency adversely affects T cell development, proliferation, TCR signaling and cell mediated immunity
Author(s) -
Shrimali Rajeev Kumar,
Irons Robert D,
Carlson Bradley A,
Park Jin M,
Hatfield Dolph L
Publication year - 2007
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.21.5.a114-b
Subject(s) - t cell , t cell receptor , immune system , biology , cd28 , cd8 , microbiology and biotechnology , immunity , cytotoxic t cell , cell growth , population , immunology , in vitro , medicine , biochemistry , environmental health
Selenium is known to enhance immune function, but its mechanism of action is not known. To elucidate the role of selenoproteins (SPs) in T cell immunity, we used loxP‐Cre technology to specifically target the removal of the selenocysteine (Sec) tRNA gene (Δ trsp ). Flow cytometric analysis in Δ trsp mice revealed that maturation of CD4+ and CD8+ T cells in thymus were reduced by 50% (p<0.0001). In spleen and lymph nodes, the CD8+ T cell population was reduced by approximately 45%. In vitro stimulation of Δ trsp T cells with anti‐CD3/CD28 had no effect on IL‐2 production, but cell proliferation was reduced by 98% (p<0.0001) and they also underwent greater apoptosis. Furthermore, Δ trsp T cells exhibit a reduced IL2‐R expression and defective phosphorylation of p44/p42 MAPK which is involved in signaling cell proliferation. IL‐4 and IL‐10 production was reduced by 75% (p<0.05, p<0.01, respectively) indicating that the lack of SPs in T cell may impair Th2 immunity. NP‐OVA immunized Δ trsp mice have reduced levels of serum Ig. Findings thus far suggest that SPs are essential for normal T cell development, TCR signaling and T cell dependent immunity. We predict and are investigating: 1) SPs through their redox potential properties protect T cells from ROS generated during signaling events of immune response, and 2) the Δ trsp T cell mice are immunocompromised. This research was supported by the Intramural Research Program of the NIH, NCI.