Biology Reference
In-Depth Information
nonhuman primates have been shown to elicit lytic activity to a variety of
targets, such as HIV- and SIV-infected cells and anti-CD3
ÿ
coated HL60
cells ( Boullier et al., 1997; Wallace et al., 1994, 1996). Kozbor et al. suggested
that Vd1 T cells respond to HIV and may be cytotoxic for HIV-infected cells
(Kozbor et al., 1993). Recently, a substantial number of Vd1 T cells from HIV-
infected donors was found to express TiA-1 and perforin, and Vd1 T-cell lines
derived from these patients display cytotoxic activity (di¨erent from lympho-
teine-activated killer [LAK] and natural killer [NK]-like activities) for anti-
CD3
ÿ
coated HL60 targets (Boullier et al., 1997).
Along with their potent cytotoxic activity, Vd1 T cells also secreted IFN-g
and tumor necrosis factor (TNF )-a. The role of these cytokines in HIV im-
munopathogenesis is not well established, and could have regulatory, protec-
tive, or deleterious functions during the course of the HIV infection (Hacker et
al., 1995; Macchia et al., 1993; Sarin et al., 1995). For example, Geissler and
colleagues demonstrated that both IFN-g and TNF-a could be implicated in
the pathogenesis of bone marrow failure during HIV infection (Geissler et al.,
1996). They showed that depletion of CD8
Vd1 T cells, but not of CD4
or CD8
ab TCR
T cells, increased the pluripotent and lineage-committed
progenitor cells colony-forming unitsÐgranulocyte-erythroid-macrophage-
megakaryocyte (CFU-GEMM), burst-forming unitsÐerythroid (BFU-E), and
colony-forming unitsÐgranulocyte-macrophage (CFU-GM) in HIV-infected
persons. Furthermore, neutralizing anti-IFN-g and anti-TNF-a antibodies re-
stored colony growth for CFU-GM in HIV infection, although direct cell con-
tact between Vd1 T cells and hematopoietic progenitor cells also contributed
to hematopoietic failure (Dobmeyer et al., 1998; Geissler et al., 1991, 1992,
1996).
Antigen Repertoire and Functional Capabilities of V
d
2 T-Cell Subset
in HIV Infection: Implications for the Immunopathogenesis of AIDS
As mentioned above, the two most signi®cant alterations in gd T cells during
HIV infection are selective expansion of Vd1 T cells associated with a decrease
in Vg9Vd2 T cells (Boullier et al., 1995).
Vg9Vd2 T cells respond to mycobacterial phosphoantigens (see ``Antigen
Repertoire and Recognition''). Wallace and co-workers showed that gd T-cell
clones isolated from SIV
ÿ
primates or HIV
ÿ
donors lyse either SIV- or HIV-
infected targets in an MHC-unrestricted manner (Wallace et al., 1994, 1996).
This lytic activity was restricted to Vg9Vd2
T cells and absent in Vd1-bearing
T cells. The fact that Vg9Vd2 T cells from HIV
ÿ
donors without previous ex-
posure to the viral antigens showed lytic activity against virus-infected cells
suggests that the antigens recognized may be of cellular origin (stress-induced)
and could constitute an important anti-HIV mechanism in healthy HIV
ÿ
per-
sons. In addition, phosphoantigen-reactive Vg9Vd2 T cells have been shown to
recognize and lyse HIV-1-infected cells inducing apoptotic death through a
perforin/granzyme pathway (Poccia et al., 1997). This could be an important
