Table 2.

Biological role of immune checkpoint markers on T cell function in HIV/SIV infection.

IC Marker	Function Mediated by HIV/SIV Infection
	CD4+ T Cell		CD8+ T Cell
PD-1	Proliferation	Impairs proliferation of HIV-specific CD4+ T cells [2,40,45]. Impairs proliferation of SIV-specific CD4+ T cells [49].	Proliferation	Impairs proliferation of HIV-specific effector memory CD8+ T cells and HIV-specific CD8+ T cells [2,9,40,44,46]. Impairs proliferation of SIV-specific CD8+ T cells [48,49].
	Cytokine secretion	Reduces IFN-γ secretion by HIV-specific CD4+ T cells [15].	Cytokine secretion	Reduces IFN-γ, IL-2, TNF-α, granzyme B, and lymphotoxin-α secretion by HIV-specific CD8+ T cells [9,15,44].
	Virus reservoirs	Contributes to HIV reservoirs in CD4+ T cells [14,17,59,60,61,62,63,67,68,69]. Contributes to SIV reservoirs in resting CD4+ central memory T cells in LNs [65].
TIGIT	Virus reservoirs	Contributes to HIV reservoirs in CD4+ T cells [17,59,60,68].	Proliferation	Impairs proliferation of HIV-specific CD8+ T cell [32]. Inhibits the proliferation of SIV-specific CD8+ T cells [32].
			Cytokine secretion	Reduces IFN-γ, TNF-α, and IL-2 production in HIV-specific CD8+ T cells [32]. Increases perforin and granzyme B production in CD8+ T cells [32]. Decreases the frequency of polyfunctional CD107a+GrzB+IFN-γ+TNF+ as well CD107a−GrzB−IFN-γ+TNF− HIV-specific CD8+ T cells [33]. Upregulates genes associated with antiviral immunity in CD8+ T cells [51]. Reduces IFN-γ secretion by SIV-specific CD8+ T cells [32].
CTLA-4	Proliferation	Reduces the proliferation of HIV-specific CD4+ T cell producing IFN-γ and IL-2 [50].	Cytokine secretion	Reduces IFN-γ, CD40L, IL-2, and TNF-α by CD8+ T cells [31].
	Cytokine secretion	Reduces IFN-γ, CD40L, IL-2 and TNF-α by CD4+ T cells [31].
	Virus reservoirs	Contributes to SIV reservoirs in memory CD4+ T cells [64,68].
LAG-3	Proliferation	Impairs HIV-specific CD4+ T cell proliferation [36].	Proliferation	Impairs HIV-specific CD8+ T cell proliferation [36].
	Cytokine secretion	Reduces IFN-γ secretion by HIV-specific CD4+ T cell [36].	Cytokine secretion	Reduces IFN-γ secretion by HIV-specific CD8+ T cell [36].
	Virus reservoirs	Contributes to HIV reservoirs in CD4+ T cells [14,17,59].
Tim-3	Proliferation	Impairs proliferation of HIV-specific CD4+ T cells [37,46].	Proliferation	Impairs proliferation of CD8+ T cells and HIV-specific CD8+ T cells [37,38,46].
	Cytokine secretion	Inhibits IFN-γ, TNF-α, and CD107a production in total and HIV-specific CD4+ T cells [37,54]. Increases IFN-γ, TNF-α, IL-2, and CD107a production in SIV-specific CD4+ T cells [55].	Cytokine secretion	Inhibits IFN-γ, TNF-α, and CD107a production in total and HIV-specific CD8+ T cells [37,54]. Decreases ability to release perforin and granzymes by HIV-specific CD8+ T cells [54]. Inhibits IFN-γ production in total and SIV-specific CD8+ T cells [38]. Increases IFN-γ, TNF-α, IL-2, and CD107a production in SIV-specific CD8+ T cells [55].
	Virus reservoirs	Contributes to HIV reservoirs in CD4+ T cells [14,58,68].
CD160	N/A		Proliferation	Impairs proliferation of HIV-specific CD8+ T cells [56]. Enhances proliferation of HIV-specific CD8+ T cells [39].
			Cytokine secretion	Inhibits IFN-γ, TNF-α, and CD107a production in HIV-specific CD8+ T cells [56]. Increases CD107a and granzyme B expression in HIV-specific CD8+ T cells [39].
2B4	Cytokine secretion	Reduces CD40L production in CD4+ T cells [31].	Proliferation	Impairs proliferation of HIV-specific CD8+ T cells [30].
			Cytokine secretion	Reduces IFN-γ, TNF-α, IL-2, and perforin in HIV-specific CD8+ T cells [30,57]. Reduces CD40L in CD8+ T cells [31].
BTLA	Cytokine secretion	Impairs BTLA-mediated suppression of IL-2 and IFN-γ production in CD4+ T cells [24].	N/A
	Virus reservoirs	Contributes to HIV reservoirs in CD4+ T cells [68].
VISTA	Cytokine secretion	Attenuates IFN-γ and TNF-α production in CD4+ T cells [10].	Cytokine secretion	Attenuates IFN-γ and TNF-α production in CD8+ T cells [10].