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Wang, C.* ; McPherson, A.J.* ; Jones, R.B.* ; Kawamura, K.S.* ; Lin, G.H.* ; Lang, P.A.* ; Ambagala, T.* ; Pellegrini, M.* ; Calzascia, T.* ; Aidarus, N.* ; Elford, A.R.* ; Yue, F.Y.* ; Kremmer, E. ; Kovacs, C.M.* ; Benko, E.* ; Tremblay, C.* ; Routy, J.P.* ; Bernard, N.F.* ; Ostrowski, M.A.* ; Ohashi, P.S.* ; Watts, T.H.*

Loss of the signaling adaptor TRAF1 causes CD8+ T cell dysregulation during human and murine chronic infection.

J. Exp. Med. 209, 77-91 (2012)
Verlagsversion Volltext DOI PMC
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The signaling adaptor TNFR-associated factor 1 (TRAF1) is specifically lost from virus-specific CD8 T cells during the chronic phase of infection with HIV in humans or lymphocytic choriomeningitis virus (LCMV) clone 13 in mice. In contrast, TRAF1 is maintained at higher levels in virus-specific T cells of HIV controllers or after acute LCMV infection. TRAF1 expression negatively correlates with programmed death 1 expression and HIV load and knockdown of TRAF1 in CD8 T cells from viral controllers results in decreased HIV suppression ex vivo. Consistent with the desensitization of the TRAF1-binding co-stimulatory receptor 4-1BB, 4-1BBL-deficient mice have defects in viral control early, but not late, in chronic infection. TGFβ induces the posttranslational loss of TRAF1, whereas IL-7 restores TRAF1 levels. A combination treatment with IL-7 and agonist anti-4-1BB antibody at 3 wk after LCMV clone 13 infection expands T cells and reduces viral load in a TRAF1-dependent manner. Moreover, transfer of TRAF1(+) but not TRAF1(-) memory T cells at the chronic stage of infection reduces viral load. These findings identify TRAF1 as a potential biomarker of HIV-specific CD8 T cell fitness during the chronic phase of disease and a target for therapy.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Chronic viral-infection; Lymphocytic choriomeningitis virus; Simian immunodeficiency virus; Receptor-associated factors; Necrosis-factor receptor; Factor-kappa-B; In-vivo; Hodgkin-lymphoma; PD-1 expression; TNF superfamily
ISSN (print) / ISBN 0022-1007
e-ISSN 1540-9538
Zeitschrift Journal of Experimental Medicine
Quellenangaben Band: 209, Heft: 1, Seiten: 77-91 Artikelnummer: , Supplement: ,
Verlag Rockefeller University Press
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Immunology (IMI)