The Negative Checkpoint Receptor TIGIT Marks Exhausted T cells During SIV Infection and Correlates...

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

CD8+ T cell

TIGIT CD155

PD1 PDL1

Proliferation Cytokine production

TCR+

-

-

Rhesus TIGIT shares 88.1% sequence homology with human TIGIT

High antigenic load environment T cell exhaustion

TIGIT expression is increased in SIV+ RMs and correlates with viral load

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

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

AcknowledgementsOregon Health & Science UniversityJonah SachaBenjamin BurwitzShaheed AbdulhaqqHelen WuJason ReedKatherine HammondReesab PathakScott Hansen

University of HawaiiLishomwa NdhlovuGlen Chew – TUAA02Tsuyoshi Fujita

Bristol-Myers SquibbAlan KormanMark Maurer