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Loss Of Protein Kinase Cθ, Bcl10, Or Malt1 Selectively Impairs Proliferation And NF-κB Activation In The CD4+ T Cell Subset1

Lara M. Kingeter, B. Schaefer
Published 2008 · Biology, Medicine

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The cytosolic proteins protein kinase Cθ (PKCθ), Bcl10, and Malt1 play critical roles in TCR signaling to the transcription factor NF-κB. Our data confirm that CD4+ T cells from PKCθ, Bcl10, and Malt1 knockout mice show severe impairment of proliferation in response to TCR stimulation. Unexpectedly, we find that knockout CD8+ T cells proliferate to a similar extent as wild-type cells in response to strong TCR signals, although a survival defect prevents their accumulation. Both CD4+ and CD8+ knockout T cells express activation markers, including CD25, following TCR stimulation. Addition of exogenous IL-2 rescues survival of knockout CD4+ and CD8+ T cells, but fails to overcome the proliferation defect of CD4+ T cells. CD4+ T cells from knockout mice are extremely deficient in TCR-induced NF-κB activation, whereas NF-κB activation is only partially impaired in CD8+ T cells. Overall, our results suggest that defects in TCR signaling through PKCθ, Bcl10, and Malt1 predominantly impair NF-κB activation and downstream functional responses of CD4+ T cells. In contrast, CD8+ T cells maintain substantial NF-κB signaling, implying the existence of a significant TCR-regulated NF-κB activation pathway in CD8+ T cells that is independent of PKCθ, Bcl10, and Malt1.
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