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life and reaches a mean of 75% in adults (Parker et al., 1990). Apart from
changes in Vg and Vd expression, there is a tendency to develop a more oligo-
clonal gd T-cell repertoire with age, which suggests an antigen-mediated selec-
tion of gd TCRs (Giachino et al., 1994).
Sites of preferential gd T-cell location in postnatal life include thymus, in-
testinal epithelium, and red pulp of the spleen (1±17% of T cells), where gd T
cells predominantly express Vd1 paired with Vg other than Vg9 (Bordessoule et
al., 1990; Casorati et al., 1989; Deusch et al., 1991; Porcelli et al., 1991; Ullrich
et al., 1990). Among IELs, gd T cells represent between 30% and 40% of all
lymphocytes. About 70% of gd TCR IELs express Vd1 and 17% Vd3 ( Deusch
et al., 1991; Spencer et al., 1989; Ullrich et al., 1991). As in peripheral blood,
intestinal gd T cells tend toward increased oligoclonality with age ( Holtmeier
et al., 1995; Van Kerckhove et al., 1992). This has been attributed to bacterial
antigen-, environmental antigen-, or neuroendocrine hormone-driven selection
(Holtmeier et al., 1995).
One unresolved issue in postnatal gd T-cell development in humans is the
extrathymic generation of gd T cells in the intestine. Generation of gd T cells
in the intestinal cryptopatches has been demonstrated in mice but it is still
unproven in humans (McVay and Carding, 1999).
gd T PHENOTYPE
gd T-Cell Morphology and Surface Markers
In general, circulating gd T cells are morphologically similar to ab T cells. In
contrast, Vd1 expressing T cells in mucosal tissues can adhere to plastic and
emit long ®lopodia when maintained in culture ( Ferrini et al., 1989; Grossi et
al., 1989).
Most gd T cells do not express CD4 or CD8 coreceptors ( Lanier et al.,
1986). A small fraction of gd T cells express CD8 (20±30%, mainly Vd1). Ex-
pression of CD4 is rare and correlates with little or no cytotoxic activity (Groh
et al., 1989; Morita et al., 1991; Scott et al., 1990). The low frequency of ex-
pression of CD4 and CD8 coreceptors in most gd T cells is consistent with the
lack of evidence for MHC restriction in antigen recognition.
Other receptors commonly expressed on the surface of ab and gd T cells in-
clude CD2, CD5, and CD7 (Faure et al., 1988; Groh et al., 1989; Kabelitz and
Conradt, 1988). CD28, the ligand for B7 (CD80/86), is absent from the major-
ity of gd T cells (Groh et al., 1989; Poggi et al., 1987). As CD28 is the main
costimulator of ab T cells, other molecules must be responsible for costi-
mulation of gd T cells. Candidates include CD40L and vitronectin. A signi®-
cant percentage of Vg9/Vd2 T cells expresses the memory marker CD45RO
(Braakman et al., 1991; Hayward et al., 1989; Miyawaki et al., 1990). These gd
T cells also constitutively express perforin and serine esterases suggesting in
vivo preactivation (Koizumi et al., 1991; Nakata et al., 1990).
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