Biology Reference
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F i g u r e 8.3. Dysregulation of Vg9Vd2 T-cell function in late stages of HIV-1 infection. Vg9Vd2
normally recognize phosphoantigens (PhosAg) and undergo activation and expansion. These re-
sponses are down-regulated in the late stages of HIV-1 infection (indicated by broken arrows). Vd2
T-cell anergy results in poor IFN-g secretion, de®cient macrophage (Mf) activation, and subsequent
lack of control of opportunistic infections (OI ). b-chemokines ( b-chemok.) display antiviral activity,
and their de®cient production in HIV
patients may contribute to lack of control of HIV replica-
tion. In addition, de®cient cytotoxic activity results in impaired elimination of infected targets.
antiviral function of gd T cells, in particular for their ability to respond quickly
in an HLA-unrestricted manner. It has been demonstrated that Vg9Vd2 from
HIV-infected patients show defective proliferative responses against phospho-
antigens and low cytotoxicity against Daudi cells when compared with Vg9Vd2
T cells from non-HIV-infected individuals (Chia et al., 1995; Wallace et al.,
1997). Defective function of gd T cells may play a role in the increased risk for
oportunistic infections during late-stage HIV infection (Fig. 8.3).
The second important function of Vg9Vd2 T cells is cytokine secretion.
Nonpeptide-reactive Vg9Vd2 T cells showed a predominant Th1 phenotype,
secreting IFN-g upon stimulation with minimal IL-4 secretion ( Follows et al.,
1992; Morita et al., 1991). In HIV-infected individuals, especially in patients
with opportunistic infections, it has been demonstrated that Vg9Vd2 T cells are
de®cient in production of IFN-g after phosphoantigen stimulation (Fig. 8.3)
(Martini et al., 2000; Boullier et al., 1997; Garcia et al., 1997). This defect in
IFN-g secretion was not reversed by IL-12 or IL-15, two potent Th1-inducing
cytokines ( Boullier et al., 1997; Garcia et al., 1997). This contrasts with the
ability of IL-12 to restore ab T-cell responses in HIV infection (Clerici et al.,
