TY  - JOUR
AU  - Wang, C
AU  - McPherson, AJ
AU  - Jones, RB
AU  - Kawamura, KS
AU  - Lin, GHY
AU  - Lang, PA
AU  - Ambagala, T
AU  - Pellegrini, M
AU  - Calzascia, T
AU  - Aidarus, N
AU  - Elford, AR
AU  - Yue, FY
AU  - Kremmer, E
AU  - Kovacs, CM
AU  - Benko, E
AU  - Tremblay, C
AU  - Routy, J-P
AU  - Bernard, NF
AU  - Ostrowski, MA
AU  - Ohashi, PS
AU  - Watts, TH
Y2  - 2021/02/05
Y1  - 2012/01/16
SN  - 0022-1007
UR  - http://hdl.handle.net/11343/260262
AB  - 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.
LA  - English
PB  - ROCKEFELLER UNIV PRESS
T1  - Loss of the signaling adaptor TRAF1 causes CD8(+) T cell dysregulation during human and murine chronic infection
DO  - 10.1084/jem.20110675
IS  - Journal of Experimental Medicine
VL  - 209
IS  - 1
SP  - 77-91
L1  - /bitstream/handle/11343/260262/PMC3260874.pdf?sequence=1&isAllowed=y
ER  -