Biology Reference
In-Depth Information
that Vg9Vd2 T cells reduce the viability of intracellular M. tuberculosis. This
inhibition of mycobacterial growth was the consequence of gd T-cell cytotoxic
activity mediated by a granule exocytosis mechanism that resulted in killing of
the intracellular pathogen ( Dieli et al., 2000).
gd
T CELLS IN HIV INFECTION
HIV is a retrovirus that infects primarily T cells and macrophages. As the in-
fection progresses, CD4
T cells are eliminated resulting in an immunocom-
promised state. The ®nal stage of the disease is characterized by development of
opportunistic infections and malignancies, responsible for the high mortality
of this infection. In healthy adults, 3±10% of peripheral blood T cells are gd
TCR
cells, of which 70±90% carry the Vg9 and Vd2 TCR and only 20±30%
express the Vd1 chain. The main alteration of the gd T cell subset in HIV-1-
infected persons is the selective expansion of the Vd1 gd T cells and a decrease
in Vg9Vd2 T cells, resulting in the reversal of the normal Vd2/Vd1 ratio. In
fact, Vd1 gd T cells constitute >70% of the gd T lymphocyte repertoire in HIV-
infected patients (Autran et al., 1989; Boullier et al., 1995; Chervenak et al.,
1997; de Paoli et al., 1991a, b; Hinz et al., 1994). Importantly, these gd T-cell
alterations correlate with overall level of immunode®ciency and occur before
the development of opportunistic infections, suggesting that it is not linked to a
challenge with environmental antigens. ( De Paoli et al., 1991). This increase
in Vd1 gd T cells in peripheral blood is a selective feature of HIV-1 infection
because it was not detected in other viral infections such as HSV-1, HSV-2, or
hepatitis B or C. Rossol and colleagues suggested that this selective Vd1 ex-
pansion may support a role of gd T cells in immunosuppression and progres-
sion of HIV infection (Rossol et al., 1998). In addition to circulating gd T-cell
changes during HIV-1 infection, alterations in IELs gd T cells have been dem-
onstrated. Nielssen et al. showed high numbers of gd T cells in duodenal
mucosa in HIV
patients; however, progressive loss of gd IELs was associated
with a short survival expectancy in late-stage AIDS ( Nilssen et al., 1996).
gd
TCR Repertoire and
gd
T-Cell Surface Markers
in HIV-Infected Persons
Flow cytometric analysis of peripheral blood lymphocytes from HIV-infected
people have demonstrated that, although the total number of gd T cells is pre-
served or even increased, the proportion of Vd1
cells is augmented (Autran et
al., 1989; Boullier et al., 1995; Chervenak et al., 1997; de Paoli et al., 1991a, b;
Hinz et al., 1994). De Maria et al. demonstrated that the alteration in the ratio
Vd2/Vd1 in peripheral blood preceded the inversion of the CD4 to CD8 ratio
in HIV-infected individuals. The same relative increase in Vd1 expression was
detected in bone marrow mononuclear cells in HIV
patients ( Rossol et al.,
1998) In addition to the characteristic Vd1 usage, changes in Vg chain usage
