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Evasion of Cytotoxic T Lymphocyte (CTL) Responses by Nef-dependent Induction of Fas Ligand (CD95L) Expression on Simian Immunodeficiency Virus–infected Cells
- Source :
- The Journal of Experimental Medicine
- Publication Year :
- 1997
- Publisher :
- Rockefeller University Press, 1997.
-
Abstract
- Inoculation of macaques with live attenuated SIV strains has been shown to protect against subsequent challenge with wild-type SIV. The protective mechanism(s) remain obscure. To study the effect in more detail, we have investigated the role of virus-specific CTL responses in macaques infected with an attenuated SIV strain (pC8), which has a four–amino acid deletion in the nef gene, as compared with the wild-type SIVmac32H clone (pJ5). Cynomolgus macaques infected with pC8 were protected against subsequent challenge with pJ5 and did not develop any AIDS-like symptoms in the 12 months after infection. The pC8-induced protection was associated with high levels of virus-specific CTL responses to a variety of viral antigens. In contrast, pJ5-infected macaques had little, if any, detectable CTL response to the viral proteins after three months. The latter group of macaques also showed increased Fas expression and apoptotic cell death in both the CD4+ and CD8+ populations. In vitro, pJ5 but not pC8 leads to an increase in FasL expression on infected cells. Thus the expression of FasL may protect infected cells from CTL attack, killing viral-specific CTLs in the process, and providing a route for escaping the immune response, leading to the increased pathogenicity of pJ5. pC8, on the other hand does not induce FasL expression, allowing the development of a protective CTL response. Furthermore, interruption of the Fas-FasL interaction allows the regeneration of viral-specific CTL responses in pJ5-infected animals. This observation suggests an additional therapeutic approach to the treatment of AIDS.
- Subjects :
- CD4-Positive T-Lymphocytes
Fas Ligand Protein
Immunology
Simian Acquired Immunodeficiency Syndrome
Clone (cell biology)
chemical and pharmacologic phenomena
CD8-Positive T-Lymphocytes
Biology
medicine.disease_cause
Jurkat cells
Article
Fas ligand
Jurkat Cells
03 medical and health sciences
0302 clinical medicine
Immune system
medicine
Animals
Humans
Immunology and Allergy
Cytotoxic T cell
GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries)
030304 developmental biology
Acquired Immunodeficiency Syndrome
Immunity, Cellular
0303 health sciences
Membrane Glycoproteins
hemic and immune systems
Articles
Simian immunodeficiency virus
Flow Cytometry
Virology
CTL
Simian Immunodeficiency Virus
CD8
030215 immunology
Subjects
Details
- ISSN :
- 15409538 and 00221007
- Volume :
- 186
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....d8e576f97f8f767d6cf65f4e3de85f53