| First Author | Kingeter LM | Year | 2008 |
| Journal | J Immunol | Volume | 181 |
| Issue | 9 | Pages | 6244-54 |
| PubMed ID | 18941215 | Mgi Jnum | J:140730 |
| Mgi Id | MGI:3814481 | Doi | 10.4049/jimmunol.181.9.6244 |
| Citation | Kingeter LM, et al. (2008) Loss of protein kinase Ctheta, Bcl10, or Malt1 selectively impairs proliferation and NF-kappaB activation in the CD4+ T cell subset. J Immunol 181(9):6244-54 |
| abstractText | The cytosolic proteins protein kinase Ctheta (PKCtheta), Bcl10, and Malt1 play critical roles in TCR signaling to the transcription factor NF-kappaB. Our data confirm that CD4(+) T cells from PKCtheta, 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-kappaB activation, whereas NF-kappaB activation is only partially impaired in CD8(+) T cells. Overall, our results suggest that defects in TCR signaling through PKCtheta, Bcl10, and Malt1 predominantly impair NF-kappaB activation and downstream functional responses of CD4(+) T cells. In contrast, CD8(+) T cells maintain substantial NF-kappaB signaling, implying the existence of a significant TCR-regulated NF-kappaB activation pathway in CD8(+) T cells that is independent of PKCtheta, Bcl10, and Malt1. |
