. Author manuscript; available in PMC: 2018 Aug 1.

Published in final edited form as: Nat Rev Immunol. 2017 Oct 9;18(2):91–104. doi: 10.1038/nri.2017.112

Table 2.

Summary of pre-clinical or ex vivo studies in infectious diseases reporting benefits of targeting inhibitory immune receptors

Infection	Cell type affected	Inhibitory Receptor	Target Species	Outcomes	Refs
HIV	CD4⁺; CD8⁺ T cells	PD-1; CTLA4 TIGIT; LAG3	Humans/Mice	Increased HIV-specific CD8+ T-cells (2 of 6 participants) Current clinical trials in malignancy underway	^{37,38,43,64,159,160}
SIV	CD8⁺ T cells	PD-1; PD-L1; CTLA4	Macaques	PD-1 blockade expands functional virus-specific CD8 T cells and prolongs survival	^38,54,59
HBV	CD4⁺; CD8⁺ T cells	PD-1; CTLA4; 2B4; TIM3	Humans (ex vivo)/mice/woodchuck	PD-1, CTLA4 & TIM3 expressed on CD4⁺ & CD8⁺ T cells from patients with chronic HBV infection. PD-1, CTLA4 & TIM3 blockade enhanced expansion and function of HBV-specific CD8 T cells in vitro.	^{84–86,89,97,98}
HCV	CD4⁺; CD8⁺ T cells	PD-1; PD-L1	Human	PD-1 is up-regulated on total and HCV-specific CD8⁺CTLs in the peripheral blood & livers of patients with chronic infection PD-L1 blockade restores functional competence of HCV-specific CTLs in vitro.	^161–164
Influenza	CD8⁺ T cells	PD-1, TIM3	Mice	PD-1 expression on influenza virus-specific CD8⁺ T cells is associated with a high-pathological infection. PD-L1 blockade in vivo reduces virus titres and increases CD8⁺ T cell number but T cell functionality was not restored. TIM3 fusion protein improved immune responses.	^165,166
TB	CD4⁺; CD8⁺ T cells	TIM3	Mice	TIM3 blockade restores T cell function and improves bacterial control, particularly in chronically infected susceptible mice	¹⁰⁶
Listeria	CD8⁺ T cells	PD-L1	Mice	PD-L1 plays an important costimulatory role for antigen-specific CD8 T cells	¹⁶⁷
Malaria	CD4⁺; CD8⁺T cells; B cells	PD-1; PD-L1; CTLA4; LAG3;TIM3	Mice	Accelerated parasite clearance. Survival from lethal disease Reduced incidence of cerebral malaria	^9,26,29,31
Toxoplasma	CD8⁺ T cells	PD-1	Mice	Blockade of the PD-1-PD-L1 reinvigorates CD8⁺T-cell responses with prevention of mortality	¹⁶⁸
Leishmania	CD4⁺; CD8⁺ T cells	PD-1, PD-L1	Mice	PD-1 blockade in vivo restored T cell proliferation and function with complete resolution of chronic lesions.	^169–171