Assays for Cytotoxicity

互联网2014-02-13

750

Among cytokine families, the tumor necrosis factor (TNF) superfamily stands out as the one that contains several members with cytotoxic activity (1 –3 ). The best characterized is the prototypic member TNF-α, which is cytotoxic to a range of tumor cells, but not to most types of normal cells (1 ,4 ). However, there are now known to be around 20 molecularly related members of the TNF superfamily, several of which induce programmed cell death, i.e., apoptosis, in particular types of normal and tumor cells (1 –3 ). The nomenclature for the members of the TNF superfamily was becoming complicated; individual members were given different names, e.g., Fas ligand, CD95 ligand, APO-1 ligand, by the competing research groups involved in their discovery. Recently, a nomenclature committee has adopted and promoted a simplified naming system; each member is designated tumor necrosis factor super family, TNFSF, with a numerical suffix. Thus, for example, TNF-α becomes TNFSF2 and Fas ligand becomes TNFSF6 (see Table 1 for the full list).

Table 1 TNF Ligand and Receptor Superfamily Members ^a

Ligands	Receptors
LT-α(TNF-β)/TNFSF1	TNF-R1/TNFRSF1A & TNF-R2/TNFRSF1B
	TNF-Rrp or LT-βR/TNFRSF3
TNF-α/TNFSF2	TNF-R1/TNFRSF1A & TNF-R2/TNFRSF1B
LT-β/TNFSF3	TNF-Rrp or LT-βR/TNFRSF3
OX40.L/TNFSF4	OX40 (CD134)/TNFRSF4
CD40.L/TNFSF5	CD40/TNFRSF5
Fas.L (APO-1L)/TNFSF6	Fas (CD95)/TNFRSF6 & DcR3/M68/TR6
CD27.L (CD70)/TNFSF7	CD27/TNFRSF7
CD30.L (CD153)/TNFSF8	CD30/TNFRSF8
4-1BB.L/TNFSF9	4-1BB (CD137)/TNFRSF9
TRAIL (APO-2.L)/TNFSF10 /TL2	DR4/TNFRSF10A /TR4 &DR5/TNFRSF10B /TR7
	DcR1/TNFRSF10C /TR5 (nonfunctional) &
	DcR2/TNFRSF10D /TR10 (nonfunctional)
	OPG/TNFRSF11B /TR1
TRANCE (OPGL)/TNFSF11 /TL9	TRANCE R/TNFRSF11A & OPG/TNFRSF11B /TR1
TWEAK (LTK)/TNFSF12 /TL8	TWEAK-R/TNFRSF12A /TR3
APRIL (TALL-2)/TNFSF13 /TL3	TACI/TNFRSF13 /TR18
BlyS (TALL-1)/TNFSF13B /TL7	TACI/TNFRSF13B /TR18 , BCMA/TNFRSF17 /TR19 & BAFF-R/TNFRSF13C
LIGHT/TNFSF14 /TL5	TNF-Rrp (LTβR)/TNFRSF3 & HVEMTNFRSF14 /TR2
VEGI/TNFSF15 /TL1	DR3/TNFRSF12? /TR3?
GITRL/TNFSF18 /TL6	GITR/TNFRSF18 /TR11
TNF-epsilon/TNFSF? /TL3	TNFRSF?
ED1/EDA/TNFSF? /TL10	EDAR/TNFRSF? /TR17 & XEDAR/TNFRSF? /TR14
TANGO-L/TNFSF?	TANGO 129/TNFRSF20? /TR12
EMILIN/TNFSF?	TNFRSF?
TRAIN-L/TNFSF?	TRAIN-R(OAF65a/APO4/TROY)/TNFRSF19 /TR15

^a Unassigned receptors:- DR6/TR9, TR13, TR16 , TACI-like/HPMK140/TR20 , TR12-like/HCFMV39/TR21 , TR21-like/HBHMF28/TR22 .