| First Author | Moebius J | Year | 2010 |
| Journal | Eur J Immunol | Volume | 40 |
| Issue | 12 | Pages | 3439-49 |
| PubMed ID | 21108466 | Mgi Jnum | J:174578 |
| Mgi Id | MGI:5139986 | Doi | 10.1002/eji.201040620 |
| Citation | Moebius J, et al. (2010) Immunoproteasomes are essential for survival and expansion of T cells in virus-infected mice. Eur J Immunol 40(12):3439-49 |
| abstractText | Immunoproteasomes containing the IFN-inducible subunits beta1i (LMP2), beta2i (MECL-1) and beta5i (LMP7) alter proteasomal cleavage preference and optimize the generation of peptide ligands of MHC class I molecules. Here, we report on an unexpected new function of immunoproteasome subunits for the survival and expansion of CD4(+) and CD8(+) T cells during viral infection of mice. The effect of immunoproteasome subunit deficiency on T-cell survival upon adoptive transfer was most prominent for the lack of LMP7 followed by MECL-1 and LMP2. The survival of T cells in uninfected mice or the homeostatic expansion after transfer into RAG-2(-/-) mice was not affected by the lack of the immunosubunits. Lymphocytic choriomeningitis virus (LCMV)-specific CD8(+) T cells lacking LMP7 or MECL-1 started to divide after transfer into LCMV-infected mice but experienced a considerable cell loss within 2 days after transfer. We provide strong evidence that the loss of immunoproteasome-deficient T cells after transfer is not a consequence of graft rejection by the host, but instead is based on the requirement for immunoproteasomes for the survival of T cells in LCMV-infected mice. Therefore, the immunoproteasome may qualify as a potential new target for the suppression of undesired proinflammatory T-cell responses. |
