Biology Reference
In-Depth Information
1992; Behr et al., 1996; Goerlich et al., 1991; Goodier et al., 1992; Ho et
al., 1994; Roussilhon et al., 1990); Leishmania (Modlin et al., 1989); HSV-1
( Bukowski et al., 1994; Maccario et al., 1995), EBV ( De Paoli et al., 1990;
Hacker et al., 1992); CMV in kidney transplant recipients ( Dechanet et al.,
1999a, b); and HIV-1 (Autran et al., 1989; Boullier et al., 1995; De Maria et al.,
1992; De Paoli et al., 1992; Hinz et al., 1994; Margolick et al., 1991).
M. tuberculosis infection is one of the diseases in which the role of gd T
cells has been studied extensively. M. tuberculosis induces gd T-cell expansion
dominated by the Vg9Vd2 subset ( Kabelitz et al., 1991). Although initially HSP
65 was thought to be the antigen responsible for this reactivity, it became clear
that small phosphate-containing molecules are the main antigens recognized by
gd T-cell responses in tuberculosis (see ``Antigen Repertoire and Recognition'').
M. tuberculosis is an intracellular pathogen that infects and resides within
mononuclear phagocytes. Thus, M. tuberculosis is an excellent model to study
the interaction between gd T cells and accessory cells. As pointed out before,
phosphoantigens can be recognized in an MHC-independent manner, not requir-
ing uptake or presentation. However, gd T-cell responses to intact M. tubercu-
losis bacilli depend on accessory cells. Both monocytes and alveolar macro-
phages were found to be e½cient accessory cells ( Balaji and Boom, 1998; Boom
et al., 1992). It has been di½cult to determine whether accessory cells function
as mere sources of costimulatory signals or if they also process and present
antigens to gd T cells. In contrast to the proposed ``surface processing model''
(discussed in ``Recognition of Phosphoantigens by Human Vg9Vd2
T Cells''),
studies with M. tuberculosis bacilli indicated that mycobacterial antigens re-
quire uptake, are processed intracellularly, and are stably presented on surface
of monocytes (Balaji and Boom, 1998).
As potent sources of IFN-g and competent cytotoxic e¨ector cells, gd T cells
may play an important role in tuberculosis infection, complementing the pro-
tective function of CD4
T cells. Some studies have tried to address the in vivo
role of gd T cells in the human immune response to M. tuberculosis. Evidence
for a role in protection was supported by demonstration of lower expansion of
gd T cells in response to heat-killed mycobacteria in patients with pulmonary or
miliary tuberculosis (Barnes et al., 1992). Although gd T cells were found in the
lung of tuberculosis patients, their proportion was not increased in comparison
to ab T cells (Schwander et al., 1996). Other studies demonstrated strong cor-
relation between the absence or loss of Vg9Vd2 T cells and manifestations of
disease (decrease in number and impaired function of blood and lung Vg9Vd2
T cells in patients versus controls) (Li et al., 1996).
The greater ability of PPD
persons compared to PPD
ÿ
people to activate
gd T cells in response to M. tuberculosis brings additional support for a role
of gd T cells in protective immunity. Furthermore, vaccination with BCG in-
creased in vitro expansion of Vg9Vd2 T cells after stimulation with M. tuber-
culosis antigens (Hoft et al., 1998).
More recently, evidence for an important role of gd T cells in protection
against M. tuberculosis came from an in vitro study. Dieli et al. demonstrated
