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Abstract
ROLE OF CD154 SIGNALLING DURING INFECTION OF MACAQUES WITH SIV
GIAVEDONI L, HODARA V, VELASQUILLO M, PARODI L
Objective: To analyze mechanisms of cellular immune responses to retroviral infections. Specifically, we studied the role of CD154, a costimulatory molecule expressed by activated CD4+ T cells that has a critical function in the interaction of T cells with dendritic cells, B cells, and macrophages.
Methods: We made a live-attenuated SIV that expressed CD154 (SIVCD154) and a control virus (SIVCNTL). In vitro studies were performed in rhesus PBMC, and in vivo experiments consisted of infecting two groups of four macaques (some of which were Mamu-A*01+), with SIVCD154 or SIVCNTL. Infection was analyzed by flow cytometry, SIV-specific cell-mediated immune responses were detected by IFN-g ELISPOT, tetramer staining and proliferation, and humoral immunity was monitored by ELISA.
Results: In vitro infection of rhesus PBMC with SIVCD154 resulted in expression of CD154 on infected T-cells, which in turn induced the appearance of activation markers on B cells; this phenomenon was not observed in PBMC infected with SIV wild-type or SIVCNTL. Interestingly, activation of T-cells by SIVCD154 did not result in increased viral replication. After infection, we isolated SIV expressing CD154 from the lymph node (LN) lymphocytes of all animals infected with SIVCD154. Activation markers on the surface of PBMC and LNC from animals from both groups did not show any significant differences, with the exception of CD69 on CD4+ T cells, B cells, and NK cells, which was present at higher levels in animals infected with SIVCNTL, even though viral loads were similar for both viruses. Cellular immune responses were stronger for animals infected with SIVCD154 at earlier time-points; these differences disappeared with time. In contrast, humoral immune responses were similar for both groups.
Conclusions: These results suggest that CD154 may be important for the induction of a primary cellular immune response early after infection, before the establishment of the chronic stage.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
90
Suggested Citation
"GIAVEDONIL, et al.
ROLE OF CD154 SIGNALLING DURING INFECTION OF MACAQUES WITH SIV.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
90"
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