Biology Reference
In-Depth Information
The gd T cells express surface receptors common on natural killer cells, the
so-called natural killer cell receptors (NKRs). There are two kinds of NKRs,
inhibitory receptors, or KIR, and activating receptors, or KARs. After binding
a particular self-human leukocyte antigen ( HLA) class I allele, KIRs transmit
inhibitory signals to killer cells (Moretta et al., 1996). In contrast, KARs rec-
ognize foreign class I alleles and activate cytolytic activity by killer cells (Lanier
et al., 1997). NKRs are expressed by the majority of Vg9Vd2 T cells but not
on the Vd1 subset. These receptors may play a role in regulation of gd T-cell
responses to bacterial phosphoantigens and yet unidenti®ed tumor antigens by
shifting the activation threshold to high antigenic doses (Carena et al., 1997;
Fisch et al., 1997; Halary et al., 1997). Some KIR identi®ed on cytotoxic gd T
cells were found to be important regulators of lysis of Daudi lymphoma cells or
virus-infected cells (Moris et al., 1999; Poccia et al., 1997). The KIR found in
gd T cells are p58.1 ( KIR2DL1), p58.2 (KIR2DL2), p70 (KIR3DL1), p140
( KIR3DL2), and CD94/NKG2A or B heterodimer (Aramburu et al., 1990;
Battistini et al., 1997; Boullier et al., 1998). The KARs are not as well de®ned
and may serve to reinforce the activity of other signaling receptors, such as
TCR and KIRs ( De Libero, 1999).
gd
T-Cell Effector Molecules And Function
The gd T cells share functional capabilities with ab T cells, i.e., cytotoxicity and
cytokine production (Haas et al., 1993; Kabelitz, 1999). gd T cells exert their
cytotoxic activity on infected cells or tumor cells ( Borst et al., 1987; Bukowski
et al., 1994). A variety of infectious agents can elicit cytotoxicity by human gd
T cells: bacteria (Mycobacterium tuberculosis, Yersinia enterocolitica) (Munk et
al., 1990; Tsukaguchi et al., 1995; Young et al., 1997), parasites (Plasmodium
falciparum, Toxoplasma gondii ) ( De Paoli et al., 1992; Troye-Blomberg et al.,
1999) and viruses (HIV, herpes simplex, and Epstein-Barr virus) ( Bukowski et
al., 1995; Maccario et al., 1993; Wallace et al., 1996). This cytotoxicity is non-
HLA restricted but involves speci®c interactions between gd TCR and target
cells (Dieli et al., 2000; Lang et al., 1995; Morita et al., 1995). The cytotoxic
activity is mediated by two major mechanisms: granule exocytosis mediated by
granzyme/perforin and/or apoptosis triggered by the Fas/FasL interaction.
Preferential use of one of these two pathways has been reported in di¨erent
diseases ( Boullier et al., 1997; Dieli et al., 2000; Troye-Blomberg et al., 1999;
Vincent et al., 1996). gd T cells, similar to ab T cells, also are a source of cyto-
kines and di¨erential production of IL-2, IFN-g or IL-4, IL-5, IL-6, and IL-10
has been described for mouse gd T cells ( Ferrick et al., 1995; Fowell et al.,
1997; Wen et al., 1998). However, in humans the dichotomy between T-helper
( Th)1 and Th2 is less clear than in mice and human gd T cells are biased to the
Th1 phenotype, being very e¨ective producers of IFN-g ( Tsukaguchi et al.,
1995). Some stimuli such as phosphoantigens result in secretion of TNF-a
(Garcia et al., 1997; Lang et al., 1995). Some IL-2 secretion by gd T cells has
been reported, but it is not su½cient to sustain the gd T-cell proliferation in
culture ( Pechhold et al., 1994; Wesch et al., 1997).
