Table 1.

Roles of CD8+NK1.1+/CD8+CD161+ Cells in Infection and Immunity.

Species	T cell subset	Disease/Model	Mechanism of action	Reference
		Viral/parasitic infections
Murine	CD8+NK1.1+	Influenza infection	10% of the lung CD8+T cells upregulate NK cell receptor NK1.1+ upon infection and offer protection	Kambayashi et al. (11)
		Influenza infection	Protection by Tc17 effector cells against influenza infection is IFN-γ dependent and accompanied by greater neutrophil influx into the lung	Hamada et al. (23)
		LCMV infection	CD8+NK1.1+ T cells escape TGF-beta control, resulting in delayed contraction and apoptosis and early pathogen response	Ruiz et al. (54)
		Listeria infection	CD8+NK1.1+ T cells offer protection by early antigen independent innate immune responses mediated by IFN-γ production and GzmB expression	Seregin et al. (55)
		Malaria	Increase in the liver cell numbers of CD8+NK1.1+ cells offer protection against liver stage Plasmodium yoelii infection	Pied et al. (56)
		Malaria	Significant increase in splenic antigen experienced, activated CD8+NK1.1+ T cells offer protection against acute Plasmodium chabaudi infection	Muxel et al. (57)
Human	CD8+CD161+	Bacterial infections	Enhanced migration and enrichment of IFN-γ secreting MAIT cells at the sites of infection helps clear the pathogen	Le Bourhis et al. (19)
		EBV/CMV/influenza	Self renewing, antigen specific CD8+CD161high memory cells express anti-apoptotic molecules and survive cytotoxic chemotherapy	Turtle et al. (3)
		HCV/HBV	Antigen specific CD8+CD161+ T cells secrete pro-inflammatory cytokines IFN-γ and TNF-α and offer protection	Northfield et al. (4)
		Viral infection	CD8+CD161+ T cells markedly enriched in the liver coexpressed IL-17 with high levels of IFN-γ and/or IL-22 and offer protection against viral infections.	Billerbeck et al. (7)
		Tumor biology
Murine	CD8+NK1.1+	Leukemia/lymphoma	Expansion of cytolytic NKT cells producing IFN-γ limits GVHD in leukemia	Baker et al., Verneris et al. (68, 69)
		Melanoma	NKT like CD8+NK1.1+ T cells exert cytotoxicity against tumor cells and MDSCs, inhibit metastasis and improve survival	Li et al. (34)
		Murine Pancreatic ductal Adenocarcinoma	Adoptive transfer of antigen experienced CD8+NK1.1 cells offer anti-tumor protection	Konduri et al. (53)
		Pancreatic Cancer	Anti-tumor effects of NKT cells is dependent upon tumor associated macrophage mediated TH1 adaptive immune response	Janakiram et al. (70)
Human	CD8+CD161+	Head and Neck cancer	In HNSCC, immune evasion is mediated by down regulation of CD161 on Th17 cells in peripheral blood, primary tumor tissue, and lymph nodes	Kesselring et al. (41)
		HPV-Oropharyngeal squamous cell cancer	Antigen specific CD161+ T cells produce IL-17 and IFN-γ in the type-1 oriented tumor microenvironment resulting in reduced tumor burden and improved overall survival	Welters et al. (75)
		Hepatocellular Carcinoma	Co-expression of CD161 and IL-7R helps maintain proliferation of CD8+PD-1+ T cells partly through enhanced expression of IL-2, TNF-α, and perforin resulting in better prognosis	Li et al. (76)
		Lymphoma	In transplant setting, host NKT cells prevented lethal GVHD while perforin producing CD8+ T cells offered graft antitumor activity	Pillai et al. (77)
		Lymphoma	IL21 promoted expansion of Th1 skewed cytotoxic CAR NKT cells offering protection	Ngai et al. (78)
		Multiple tumors	KLRB1, the gene encodign CD161 is associated with favorable outcomes against multiple tumor models	Gentles et al., Braud et al. (72, 73)
		Multiple tumors	The potential immunoregulatory role of CD4+ CD161+ cells is mediated through soluble factors, high IL-10, IL-4, and TGF-β resulting in disease progression	Iliopoulou et al. (79)
		NSCLC	Tumor infiltrating CD8+CD161+ interact with LLT1 expressing germinal center B cells within TME resulting in improved survival	Braud et al. (73)
		Pediatric Leukemia	iNKT cell subsets in hHSCT recipients contribute to the maintenance of the remission state, possibly through the provision of antitumor cytokine IFN-γ.	de Lalla et al. (80)
		Autoimmunity
Human	CD8+CD161+	Autoimmune diseases	IL-17 producing Th17 cells mediate tissue inflammation and autoimmune progression in gut, joints, and brain by secreting inflammatory cytokines like IL-23	Cosmi et al., Kleinschek et al., Lock et al., Tzartos et al., Annibali et al. (60–64)
		Systemic Lupus Erythematosus	Abnormalities in the frequencies and levels of CD161 expression on CD8+ T cells and NKT cells correlate to the pathogenesis of SLE.	Park et al. (67)