Biology Reference
In-Depth Information
1993). A cause of failure in phosphoantigen-reactive gd T-cell responses in
HIV infection has been attributed to a lack of IL-2 secretion resulting from
CD4
T-cell de®ciency Th1 subset. Wesch et al. showed that the Vg9Vd2 defect
was restored by low concentrations of exogenous IL-2 ( Wesch et al., 1998).
Thus, the authors attributed the gd T-cell defect to absence or functional anergy
of Mycobacteria-reactive Th1 CD4 T cells. In contrast, Poccia and colleagues
showed that the Vg9Vd2 population from HIV-infected individuals displays
selective anergy for mycobacterial antigens that cannot be reversed by IL-2.
This defect correlated with a defect in the a-chain IL-2R (CD25) expression
(Poccia et al., 1996). gd T-cell functional alteration was observed in HIV
persons before CD4 counts dropped and was associated with an increase in Vd1
T cells ( Boullier et al., 1995; Poccia et al., 1996). Three possible explanations
have been proposed to explain the Vg9Vd2 cytokine and other functional de-
fects in HIV infection ( Boullier et al., 1999):
1. Decreased CD25 expression by anergic Vd2 T cells.
2. Abnormal expression of KIRs, which transmit negative signals upon
TCR engagement with the speci®c ligand (Carena et al., 1997).
3. Chronic activation (``superantigenic-like activity'') and functional anergy
by unknown ligands. This is related to the persistent activation of the
immune system caused by HIV and subsequent accumulation of blast
cells, which can be potent stimulators of Vd2 T cells ( Halary et al., 1997).
Candidates for this chronic stimulation are cellular antigens induced or
modi®ed by viral infection. It has been suggested that this functional
anergy may represent a regulatory mechanism to down-regulate auto-
immune Vd2 T-cell reactions ( Boullier et al., 1999).
Another important functional capability of gd T cells is secretion of antiviral
factors. Poccia and colleagues reported that phosphoantigen-reactive Vg9Vd2T
cells suppress HIV replication in vitro by releasing C-C chemokines (MIP-1a,
MIP-1-b, RANTES, and SDF-1) and suggest that gd T cells may have a role
in natural protection against HIV infection (Poccia et al., 1999). Similarly, a
model of simian immunode®ciency showed that gd T cells secrete b-chemokines
that bind to CCR5, preventing SIV (or HIV ) infection ( Lehner et al., 2000).
Role and Significance of
gd
T Cells in HIV Infection
The overall role of gd T cells in HIV infection remains unclear. The presence of
functional gd TCR T cells may be important because they normally do not
express CD4, an essential component for viral fusion. HIV-reactive gd T cells
could respond to infected cells without the threat of infection by the T-cell
tropic virus. However, the signi®cance of Vd1 and Vd2 T cells may di¨er giving
the many biological di¨erences between these two subsets. For example,
although circulating Vd1 T cells are normally underrepresented and nonfunc-
