HIV infection of monocytes-derived dendritic cells inhibits Vγ9Vδ2 T cells functions

• Published in: PloS one 2014, Vol.9 (10), p.e111095-e111095
• Main Authors: Sacchi, Alessandra, Rinaldi, Alessandra, Tumino, Nicola, Casetti, Rita, Agrati, Chiara, Turchi, Federica, Bordoni, Veronica, Cimini, Eleonora, Martini, Federico
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Anergy; Antigen-presenting cells; Antigens; Antigens, CD - metabolism; Antigens, Differentiation, T-Lymphocyte - metabolism; B7-2 Antigen - metabolism; Biology and Life Sciences; CCR5 protein; CD69 antigen; CD86 antigen; Cell activation; Cell Proliferation; Cells, Cultured; Coculture Techniques; Crosstalk; Cytokines; Cytokines - metabolism; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - virology; Histocompatibility antigen HLA; HIV; HIV Infections - blood; HIV Infections - immunology; HIV-1; Human immunodeficiency virus; Humans; Immune response; Immune System; Immunity, Innate; Immunology; Infections; Infectious diseases; Laboratories; Lectins, C-Type - metabolism; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Medicine and health sciences; Monocytes; Monocytes - cytology; Phenotype; Phenotypes; Receptors, Antigen, T-Cell, gamma-delta - immunology; T cell receptors; Trends; Tuberculosis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0111095

DCs act as sentinel cells against incoming pathogens and represent the most potent antigen presenting cells, having the unique capability to prime naïve T cells. In addition to their role in induction of adaptive immune responses, DC are also able to activate innate cells as γδ T cells; in particular, a reciprocal crosstalk between DC and γδ T cells was demonstrated. However, whether HIV infection may alter DC-Vγ9Vδ2 T cells cross-talk was not yet described. To clarify this issue, we cultured activated Vγ9Vδ2 T cells with HIV infected monocyte derived DC (MoDC). After 5 days we evaluated MoDC phenotype, and Vγ9Vδ2 T cells activation and proliferation. In our model, Vγ9Vδ2 T cells were not able to proliferate in response to HIV-infected MoDC, although an up-regulation of CD69 was observed. Upon phosphoantigens stimulation, Vγ9Vδ2 T cells proliferation and cytokine production were inhibited when cultured with HIV-infected MoDC in a cell-contact dependent way. Moreover, HIV-infected MoDC are not able to up-regulate CD86 molecules when cultured with activated Vγ9Vδ2 T cells, compared with uninfected MoDC. Further, activated Vγ9Vδ2 T cells are not able to induce HLA DR up-regulation and CCR5 down-regulation on HIV-infected MoDC. These data indicate that HIV-infected DC alter the capacity of Vγ9Vδ2 T cells to respond to their antigens, pointing out a new mechanisms of induction of Vγ9Vδ2 T cells anergy carried out by HIV, that could contribute to immune evasion.