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gut from Vd1 IELs (Boullier et al., 1997). Vd1 T cells from these two sites
shared features such as restricted Vd1-Jd1 rearrangements, decreased expression
of CD62-L, and absence of CD28 expression. In addition in vitro studies have
shown that HIV infection of monocytes can disrupt endothelial monolayers,
thereby increasing endothelial permeability (Dhawan et al., 1995). Further-
more, intestinal epithelia has been shown to support HIV and simian im-
munode®ciency virus (SIV ) replication and could constitute a repository of
virus (Veazey et al., 1998). Interestingly, Vd1-Jd1 T cells increase in intestinal
epithelia and there may be an association with survival in advanced HIV
patients (Nilssen et al., 1996). Taken together, these reports indicate that the
activated Vd1 T cells detected in peripheral blood of HIV-infected persons may
represent a subset derived from gd IELs. The recently described reactivity of gd
IELs to nonclassical MHC class Ib molecules, and their capacity to lyse cells
that express stress-induced antigens may have important implications in HIV
pathogenesis (Groh et al., 1998, 1999).
Other authors have demonstrated an increase in absolute number and per-
centage of gd T cells in bronchoalveolar lavage recovered from HIV patients
with CD8
alveolitis (Agostini et al., 1994, 1995). In this study, the pulmonary
T-cell subset expressed Vd2 and CD45RO and 30% coexpressed CD8. Inter-
estingly, the increase in the Vd2/Vd1 ratio in the lung correlated with decreased
Vd2/Vd1 cell ratio in peripheral blood and may re¯ect redistribution of Vd2
cells to speci®c organs during HIV infection. The sequestration of Vd2 T cells in
lung could lead to an increase in the proportion of Vd1 T cells in the peripheral
blood (Agostini et al., 1994).
A di¨erent explanation for the origin and activation of Vd1 T cells in
peripheral blood of HIV
individuals was proposed by Hyjek and colleagues
(Hyjek et al., 1997). These authors found that Vd1 clones isolated from HIV
individuals produced IFN-g and showed cytotoxic activity in response to lym-
phoblastoid cell lines ( LCLs) and peripheral blood B cells from HIV
patients
but not to LCLs or B cells from HIV
ÿ
controls. Furthermore, the stimulatory
ability of B cells from HIV
patients was associated with expression of activa-
tion markers (CD38) and Ig production, suggesting that Vd1 expansion might
be a consequence of functional and phenotypic alterations of B cells. Interest-
ingly, Vd1 expansion could be triggered by recognition of a speci®c ligand on
the surface of chronically activated B cells (see below), and thus Vd1 T cells
may have a role in immune surveillance for B cell lymphomas, which develop
with increasing frequency in end-stage HIV infection.
In conclusion, di¨erent explanations have been proposed for the character-
istic Vd1 expansion in HIV infection: a) Vd1 T cells may be derived from gd
IELs; b) the increase in Vd1/Vd2 ratio in blood is a consequence of redistribu-
tion of the Vd2 subset to speci®c organs; and c) Vd1 expand as a consequence
of B-cell activation and expression of gd stimulatory antigens on the surface of
B cells. Further studies will need to determine which of these three models is the
most likely explanation for the marked expansion of Vd1 T cells.
