Journal of Immunology Research

Review Article

The Role of NK Cells in Pig-to-Human Xenotransplantation

Table 2

Proven strategies to overcome NK cytotoxicity against pig endothelial cells.


Target	Approach	NK source	Effect	Reduction (%)	Ref

αGal GT	In vitro knockout pEC lines	IL2-NK cells, NK92 Fresh NK cells, Fresh NK cells	No effect CMC ↓ ADCC ↓ nAb/CML	NA 77–90 86	[46, 126]
	Gal knockout pigs	IL2-NK cells, Fresh NK cells Fresh NK cells	No effect in CMC ↓ ADCC ↓ nAb/CML	NA 70 80	[47, 124]
	siRNA in pEC	NK92 cell line	No effect CMC ↓ ADCC	NA 30–40	[125]

Masking of sugar xenoantigens	Transfections of α(1,2)-fucosyltransferase in pECs	Fresh NK cells	↓ CMC	47	[119]
Masking of sugar xenoantigens	Treatment of pECs with DXS	NK92	↓ CMC inh. C’ deposition	25–47	[135]

HLA class I molecules	HLA-E transfection in pEC	IL2-NK cells	↓ CMC	15–60	[150, 151]
	HLA-E transgenic pigs	IL2-NK cells	↓ CMC ↓ IFNγ production	8–30 40	[15]
	HLA-G1 transfection in pEC	IL2-NK cells, NK92 and NK cell clones	↓ CMC ↓ rolling/adhesion No effect in ADCC	20–45 25–75 NA	[141, 142, 150, 187]
	Soluble HLA-G1	NK92 Fresh PBMC	↓ CMC ↓ CMC	31–83 24	[145]
	HLA-Cw3 transfection in pEC	NK cell clones	↓ CMC	12–70	[136]
	HLA-Cw4 transfection in pEC	NK cell clones	↓ CMC	58	[139]
	HLA-B27 transfection in pEC	NK cell clones	↓ CMC	~30	[136]

Apoptosis induction	PK15, human FasL transfection	PBL	↓ ADCC	34–42	[108]
	PK15, human FasL transfection	PBL, LAK	↓ ADCC ↓ CMC	54 74	[127]
	pEC, human FasL transfection	IL2-NK cells	No effect CMC ↑ apoptosis NK cells	0	[129]
	pEC, pig FasL transfection	IL2-NK cells	↓ CMC ↓ FasL apoptosis	26 23	[128]

Apoptosis resistance	Bcl-2 transfection in PK15	PBL	↓ FasL apoptosis ↓ ADCC	62 50	[132]
Apoptosis resistance	Bcl-2^mut transfections in pEC	IL2-NK cells	No effect CMC	0	[110]

ADCC: antibody-dependent cell-mediated cytotoxicity; αGal GT: alpha1,3-galactosyltransferase; C’: complement; CML: complement-mediated lysis, CMC: cell-mediated cytotoxicity; DXS: dextran sulfate; HLA: human leukocyte antigen; IFNγ: interferon gamma; inh.: inhibition; LAK: lymphokine-activated killer; NA: not applicable; nAb: natural antibody; PBL: peripheral blood lymphocytes; PBMC: peripheral blood mononuclear cells; pEC: porcine endothelial cells; PK15: pig kidney cell line; siRNA: short interfering RNA; ↓: reduction.