Mechanisms associated with thymocyte apoptosis induced by simian immunodeficiency virus.
Despite considerable research, the mechanisms by which HIV disrupts thymic function remain controversial. We have described the phenotypic changes that occur in the thymus of SIV-infected macaques during acute SIV infection. In this study, we analyzed the effects of SIV infection on apoptotic pathways in thymic tissue from newborn macaques infected with SIV. Thymocyte apoptosis was accompanied by a modest increase in surface Fas expression, a profound decrease in the frequency of bcl-2-positive cells, as well as the amount of bcl-2 per cell. With control of viral replication, levels of bcl-2 and Fas returned to baseline together with a return to basal levels of apoptosis. In the thymus, SIV infection resulted in depletion of CD4+CD8+ thymocytes, an increase in apoptosis of thymocytes, and a down-regulation of MHC class I molecules. These changes peaked 14-21 days after infection at or just after peak viremia. This data further suggests disruption of the antiapoptotic pathway regulated by bcl-2 plays a critical role in SIV-induced apoptosis of thymocytes.
Rosenzweig
M
M
Divisions ofImmunology and Pathology, New England Regional Primate Research Center, Harvard Medical School, Southborough, MA 01772, USA. michael_rosenzweig@hms.harvard.edu
Connole
M
M
Forand-Barabasz
A
A
Tremblay
M P
MP
Johnson
R P
RP
Lackner
A A
AA
D000208:Acute Disease; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology; D053222:Fas Ligand Protein; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D016130:Immunophenotyping; D008024:Ligands; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D019014:fas Receptor / Q000096:biosynthesis / Q000378:metabolism
D053222:Fas Ligand Protein; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor