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Abstract
RELATIVE DYNAMICS OF SIV REPLICATION AND IMMUNE RECOGNITION: DELAYED INFILTRATION OF ANTI-SIV CTLS ALLOWS VIRAL ESCAPE
BLANCOU P
Background: In HIV and SIV infection, viral replication is principally contained in the sites of immune responses as germinal centers in the secondary lymphoid organs. These sites are usually invaded with CD8+ T cells, most of which being anti-viral CTLs. However, despite vigorous cell mediated response to human and simian immunodeficiency viruses (HIV/SIV) the immune system is unable to eliminate the pathogen leading to persistent infection and disease.
Methods: To understand the lack of efficiency of SIV specific immune responses, the kinetics of the infiltration of immune response sites were investigated using delayed type hypersensitivity reaction (DTH) as a model for immune reaction. BCG immunised, SIV infected macaques were subjected to serial intra-dermal injections of purified protein derived of Mycobacterium tuberculosis (PPD) to initiate DTH. During the immunisation period and after SIV infection, PPD specific CD4+ and SIV-specific CD8+ T cell repertoires were analysed. At sacrifice, skin patches corresponding to the injection sites were dissected out and tested for the presence of anti-PPD, anti-SIV specific T cells as well as for viral replication.
Results: Anti-PPD T cell and SIV replication were detected as early as 12 hours after the initiation of DTH reaction. Anti-SIV T cells could be identified only after 24 hours post-PPD injection concomitantly to a suppression of SIV replication. This infiltration is associated with perforin and granzyme transcription suggesting CTL activity.
Conclusions: Anti-SIV CTLs are thus infiltrating the DTH sites at least 12 hours after the initiation of local SIV replication allowing viral dissemination within the immune reaction site. This finding suggests that, even in the presence of a huge local CTL response infected antigen-specific CD4 T cells can escape from the site of immune activation to re-seed the pool of resting SIV-infected peripheral T cells.
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The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
87
Suggested Citation
"BLANCOU P
RELATIVE DYNAMICS OF SIV REPLICATION AND IMMUNE RECOGNITION: DELAYED INFILTRATION OF ANTI-SIV CTLS ALLOWS VIRAL ESCAPE.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
87"
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