Cross-talk between HIV-exposed DC and gamma-delta T cellspreclinical study dataset
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.
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- organism type
- experimental design type
- stimulus or stress response experiment