Regulatory T Cells Diminish HIV Infection in Dendritic Cells - Conventional CD4(+) T Cell Clusters.
Formation of immunological synapses (IS) between dendritic cells (DCs) and conventional CD4(+) T cells (Tcon) is critical for productive immune responses. However, when DCs are HIV-infected such synapses are critical to establish HIV infection. As regulatory T cells (Treg) control DC-Tcon interactions, we inquired whether Treg might interfere with DC to Tcon HIV infection. We developed a model, using monocyte-derived DC infected with R5-HIV, and cultured with Tcon in the presence or absence of autologous Treg, using the physiological ratio of 1 Treg for 10 Tcon. Cultures containing Treg significantly decreased HIV infection in DC:T cell clusters. Notably, Treg appear to have an effect on the quality of the IS, as Treg decreased actin polymerization and DC maturation. Importantly, Treg decreased the trafficking of HIV punctate to the IS. Further, CD152 and cyclic adenosine monophosphate were critical Treg effector molecules, as their individual or simultaneous blockade abolished Treg activity, however no additive effect was found. Together, these data suggest that Treg can reduce HIV dissemination, which may be beneficial to the host in the early stages of infection.
Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Research Foundation , Cincinnati, OH , USA ; Immunology Graduate Program, College of Medicine, University of Cincinnati , Cincinnati, OH , USA.
Maria E
ME
Moreno-Fernandez
Institute for Virology, University Hospital Essen, University Duisburg-Essen , Essen , Germany.
Jara J
JJ
Joedicke
Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Research Foundation , Cincinnati, OH , USA.
Claire A
CA
Chougnet
CTLA-4; HIV-1; actin cytoskeleton; cyclic AMP; dendritic cells; regulatory T cells