Immunoproteasomes are essential for survival and expansion of T cells in virus-infected mice

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Moebius_151545.pdf
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2010
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Moebius, Jacqueline
Broek, Maries van den
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European Journal of Immunology. 2010, 40(12), pp. 3439-3449. ISSN 0014-2980. eISSN 1521-4141. Available under: doi: 10.1002/eji.201040620
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Immunoproteasomes containing the IFN-inducible subunits β1i (LMP2), β2i (MECL-1) and β5i (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.

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Fachgebiet (DDC)
570 Biowissenschaften, Biologie
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Cytotoxic T lymphocytes, Immunoproteasome, LCMV, MHC class I
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ISO 690MOEBIUS, Jacqueline, Maries van den BROEK, Marcus GRÖTTRUP, Michael BASLER, 2010. Immunoproteasomes are essential for survival and expansion of T cells in virus-infected mice. In: European Journal of Immunology. 2010, 40(12), pp. 3439-3449. ISSN 0014-2980. eISSN 1521-4141. Available under: doi: 10.1002/eji.201040620
BibTex
@article{Moebius2010-12Immun-15154,
  year={2010},
  doi={10.1002/eji.201040620},
  title={Immunoproteasomes are essential for survival and expansion of T cells in virus-infected mice},
  number={12},
  volume={40},
  issn={0014-2980},
  journal={European Journal of Immunology},
  pages={3439--3449},
  author={Moebius, Jacqueline and Broek, Maries van den and Gröttrup, Marcus and Basler, Michael}
}
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