the negative checkpoint receptor tigit marks exhausted t cells during siv infection and correlates...
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TIGIT expression is increased in SIV+ RMs and correlates with viral loadTRANSCRIPT
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The Negative Checkpoint Receptor TIGIT Marks Exhausted T cells During SIV Infection and
Correlates with SIV Disease Progression
Gabriela WebbVaccine and Gene Therapy Institute
Oregon Health and Science University
July 21, 2015
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CD8+ T cell
TIGIT CD155
PD1 PDL1
Proliferation Cytokine production
TCR+
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Rhesus TIGIT shares 88.1% sequence homology with human TIGIT
High antigenic load environment T cell exhaustion
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TIGIT expression is increased in SIV+ RMs and correlates with viral load
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TIGIT is also found on SIV-specific CD8+ T cells in RMs with full cART suppression of SIV viremiaSIV-specific CD8+ T cells co-express TIGIT & PD-1
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TIGIT+ CD8+ T cells produce less IFNγ when stimulatedSingle and dual blockade of PDL1 and TIGIT restores CD8+ T cellproliferation
Summary• TIGIT is expressed on SIV-specific CD8+ T cells and proliferative capacity can be restored
with single or dual blockade
• Rhesus TIGIT in SIV infection recapitulates what is observed with human TIGIT in HIV infection Glen Chew (TUAA02 Rm 211-214)
• TIGIT/PD1 blockade could be used in conjunction with “shock and kill” approaches
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AcknowledgementsOregon Health & Science UniversityJonah SachaBenjamin BurwitzShaheed AbdulhaqqHelen WuJason ReedKatherine HammondReesab PathakScott Hansen
University of HawaiiLishomwa NdhlovuGlen Chew – TUAA02Tsuyoshi Fujita
Bristol-Myers SquibbAlan KormanMark Maurer