Biology Reference
In-Depth Information
compatibility complex (MHC) molecules, the range of antigens recognized by
gd T cells remains poorly de®ned, but includes nonpeptidic compounds such as
small phosphorylated molecules (Constant et al., 1994; Tanaka et al., 1994).
The recognition of peptide or nonpeptidic moieties seems to be non-MHC re-
stricted and may not require antigen processing or presentation ( Lang et al.,
1995; Morita et al., 1995).
Fourth, gd T cells di¨er from ab T cells in the expression of the MHC re-
ceptors CD4 and CD8. Most gd T cells in peripheral blood or tissues express
neither CD4 nor CD8 (Groh et al., 1989; Lanier et al., 1986; Scott et al., 1990).
A small proportion of peripheral blood gd T cells expresses CD8, and CD4
expression is rare (Moretta et al., 1988). Functional capabilities of gd T cells are
similar to ab T cells and include cytotoxicity and cytokine secretion. However,
gd T cells may have unique functions such as the regulation of epithelial growth
and immunoregulatory functions. gd T cells may have a role in regulation of
antibody production and isotype switching (Hacker et al., 1995; Horner et al.,
1995; Munk et al., 1994, 1995; Rajagopalan et al., 1992). gd T cells were also
implicated in regulating ab T-cell development and modulating ab T-cell e¨ec-
tor function. In vitro experiments with transgenic mice in which TCR g gene
expression was modi®ed and studies with anti-pan-TCR-d monoclonal anti-
bodies in mice showed altered thymic development and increased peripheral ab
T-cell responses, such as higher proliferation and interleukin (IL)-2 production
(Ferrick et al., 1989a, b, c, 1990, 1991; Kaufmann et al., 1993). In vivo deple-
tion of gd T cells has been shown to alter T-cell-dependent hypersensitivity,
tolerance, and host resistance to pathogens, suggesting a role for gd in regu-
lation of ab TCR ( Vincent et al., 1996). This regulatory mechanism may be
mediated by Fas/Fas ligand ( Fas-FasL) interaction and apoptosis and may be
important to restrict responses of ab T cells and other Fas
e¨ector cells (Born
et al., 1999). In addition, gd T cells have been implicated in regulation of
early and late stages of in¯ammation in di¨erent diseases such as in¯uenza,
listeriosis, and mycobacterial infections (Carding, 1990; Carding et al., 1990a;
D'Souza et al., 1997; Fu et al., 1994; Hsieh et al., 1996). Furthermore, a role in
regulation of tolerance to ingested or inhaled antigens and tissue grafts has also
been described for gd T cells (Fujihashi et al., 1990, 1997; McMenamin et al.,
1991, 1994; Wildner et al., 1996; Vaessen et al., 1996; Vandekerckhove et al.,
1990). A role for gd T cells has been described in numerous human diseases,
including bacterial, protozoal, and viral infections, tumor immunity, and auto-
immune disorders such as rheumatoid arthritis and systemic lupus erythe-
matosus.
THE
gd
TCR AND THE
gd
GENE FAMILIES
Human CD3
T cells express one of two TCR heterodimers: either an a chain
with a b chain (abTCR
T cells) or a g chain combined with a d chain
(gdTCR
T cells). The g and d chains consist of one variable region and one
