Cross-talk between HIV-exposed DC and gamma-delta T cells
Data has been obtained on the effect of exposure of DCs or gamma-delta T lymphocytes to HIV-1 and on the miR profile expressed in HIV-exposed DCs.
Based on our previous findings demonstrating a bidirectional activating interaction between immature MDDCs and gamma-delta T lymphocytes (Conti et al., JI. 2005), as well as on the demonstration that HIV-1 exposed MDDCs exhibit an impaired functional maturation (Fantuzzi et al., J Virol 2004), we are currently investigating whether exposure of DCs or gamma-delta T lymphocytes to HIV-1 can directly modulate their functions or interfere with their cross-talk. Preliminary results indicated that, although virus exposure of gamma-delta T cells does not significantly affect their properties, HIV-exposed DCs exhibit a reduced capacity to deliver activation and proliferative signals to gamma-delta T lymphocytes. Moreover, a dysregulated pattern of cytokines and chemokines produced by both cell populations is observed in the presence of the virus.
Our preliminary results indicating that HIV-exposed MDDCs exhibit a reduced capacity to deliver activation and proliferative signals to gamma-delta T lymphocytes have been reproduced in a statistically significant number of donors during this year. In particular, we have observed that gamma-delta T cells co-coltured with virus-exposed DCs exhibit a reduced capacity to proliferate in response to phosphoantigens and to produce IFN-?. Reciprocally, HIV-1-exposed DCs co-coltured with activated gamma-delta T lymphocytes undergo phenotypic maturation but are impaired in IL-12 production. In contrast, direct exposure of lymphocytes to the virus does not significantly affect their properties. A preliminary analysis of the miR profile expressed in HIV-exposed DCs has also been carried out indicating that interaction of these cells with the virus rapidly induces the modulation of a number of miRs.
A further characterization of the effects of HIV-1 on the functional properties of both cell populations will be performed, and in particular it will be analyzed:
(a) the capacity of virus-exposed DCs to recruit resting gamma-delta T cells;
(b) the role of activated lymphocytes in controlling HIV-1 replication in DCs;
(c) whether active virus replication in these cells is needed to achieve the above described effects;
(d) the role of HIV-modulated miR in DC functions.
data set
preclinical study dataset
Role of cytokine environment and cytokine receptor expression in human monocytes in the generation of functionally distinct dendritic cells.
Human immunodeficiency virus type 1 gp120 induces abnormal maturation and functional alterations of dendritic cells: a novel mechanism for AIDS pathogenesis.
chemokine
gamma-delta t cell
immature dendritic cell
Biomaterial
HIV-1
Lucia Conti
Sandra Gessani
Gamma-delta T lymphocytes exposed to HIV-1
monocyte-derived DCs
stimulus or stress response experiment