Immunoproteasomes are essential for survival and expansion of T cells in virus-infected mice.
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.
Division of Immunology, Department of Biology, Constance University, Konstanz, Germany.
Jacqueline
J
Moebius
Maries
M
van den Broek
Marcus
M
Groettrup
Michael
M
Basler
D000818:Animals; D001117:Arenaviridae Infections / Q000188:drug therapy / Q000276:immunology*; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D008217:Lymphocytic choriomeningitis virus; D051379:Mice; D018345:Mice, Knockout; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology
D015704:CD4 Antigens; D016827:CD8 Antigens; D004268:DNA-Binding Proteins; D015395:Histocompatibility Antigens Class I; C499308:Rag2 protein, mouse; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex; C490920:Psmb10 protein, mouse