Biology Reference
In-Depth Information
chains were detected as early as in the 5th week. During the ®rst 12 weeks of
gestation, gd T cells are the only T cells detected in fetal liver. These primitive gd
T cells express predominantly Vg9/Vd2 TCR and the Vg9 chain shows limited
structural diversity (McVay and Carding, 1996; Carding et al., 1990b). Inter-
estingly, these canonical receptors are functional and show the same antigen
speci®city as adult Vg9/Vd2 T cells, i.e., they respond to mycobacteria by pro-
liferating and with cytokine secretion (Davodeau et al., 1993). On the other
hand, productive rearrangements and expression of both Vd and Vg chains
have been described in fetal gut by the 6th week (McVay et al., 1998; Spencer et
al., 1986). By week 8, the Vd chain repertoire di¨ers between liver and gut, with
Vd1 being the dominant transcript in the intestine (Holtmeier et al., 1997). The
Vd1 transcripts generated by the 6th to 8th week in gut have extensive junc-
tional diversity (McVay et al., 1998). The origin of these primitive gd T cells
detected in the gut is not clear, and three possibilities have been proposed: a)
they are generated in situ (McVay et al., 1998); b) they tra½c from the liver
(McVay and Carding, 1999); and c) they are maternally derived (Mincheva-
Nilsson et al., 1997; White et al., 1994).
Fetal liver-derived progenitors seed the thymic rudiment by the 8th week of
gestation ( Haynes and Heinly, 1995; Lobach and Haynes, 1987). The exact role
of the thymus in gd T-cell development is not clear. Some studies suggest that
some fetal-derived gd TCR-bearing cells could migrate and seed the thymus
(McVay et al., 1998). The thymus then would be a place to mature gd T cells
with already rearranged TCR genes. Changes in the pro®le of Vd gene expres-
sion during thymic development and the ®nding of TCRD and TCRG genes in
germ-line con®guration suggest that thymus also can have a role in the gen-
eration, di¨erentiation, and thymic selection of progenitor cells (Blom et al.,
1998; Krangel et al., 1990; McVay et al., 1991a, b).
Thus, gd T cells seem to be originating from progenitor cells in both extra-
thymic sites and in the thymus during fetal development.
gd
T-Cell Repertoire Changes in Postnatal Life and Varies in
Different Tissues
In adults, gd T cells represent about 5% of CD3
cells in peripheral blood. Be-
tween 50% and 98% of the circulating gd T cells express Vd2(TRDV2-DJ1-
DC ) paired with Vg9(TRGV9-GJP-GC1) and a minority (3±9%) have TCRs
with either Vd1orVd3 elements (Jitsukawa et al., 1987; Lanier et al., 1988;
Moretta et al., 1988; Peyrat et al., 1995; Triebel and Hercend, 1989). This bias
toward the expression of Vg9Vd2 T cells is not observed in cord blood, where
the diversity of gd TCRs is broader (Morita et al., 1994; Parker et al., 1990).
The gd T cells represent approximately 2% of CD3
cells in umbilical cord
blood, with 50% expressing Vd1 and 25% carrying Vd2. Interestingly, Vd1 cells
remain predominant in thymus at all ages (65% Vd1, 17% Vd2) whereas Vd1
expression in peripheral blood decreases from 50% at birth to <10% by the
ninth decade of life. Vd2 expression starts to increase during the ®rst decade of
