Simian immunodeficiency virus (SIV)-specific CTL are present in large numbers in livers of SIV-infected rhesus monkeys.
The immunopathogenesis of AIDS-associated hepatitis was explored in the SIV/rhesus monkey model. The livers of SIV-infected monkeys showed a mild hepatitis, with a predominantly CD8+ T lymphocyte infiltration in the periportal fields and sinusoids. These liver-associated CD8+ T cells were comprised of a high percentage of SIV-specific CTL as defined by MHC class I/Gag peptide tetramer binding and Gag peptide epitope-specific lytic activity. There was insufficient viral replication in these livers to account for attracting this large number of functional virus-specific CTL to the liver. There was also no evidence that the predominant population of CTL were functionally end-stage cells trapped in the liver and destined to undergo apoptotic cell death in that organ. Interestingly, we noted that liver tetramer-binding cells showed an increased expression of CD62L, an adhesion molecule usually only rarely expressed on tetramer-binding cells. This observation suggests that the expression of specific adhesion molecules by CTL might facilitate the capture of these cells in the liver. These results demonstrate that functional SIV-specific CD8+ T cells are present in large numbers in the liver of chronically SIV-infected monkeys. Thus, the liver may be a trap for virus-specific cytotoxic T cells.
Schmitz
J E
JE
Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. jschmitz@caregroup.harvard.edu
Kuroda
M J
MJ
Veazey
R S
RS
Seth
A
A
Taylor
W M
WM
Nickerson
C E
CE
Lifton
M A
MA
Dailey
P J
PJ
Forman
M A
MA
Racz
P
P
Tenner-Racz
K
K
Letvin
N L
NL
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000032:analysis* / Q000235:genetics; D015683:Gene Products, gag / Q000276:immunology; D006520:Hepatitis, Animal / Q000276:immunology / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D016130:Immunophenotyping; D019041:L-Selectin / Q000096:biosynthesis / Q000097:blood; D008099:Liver / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D018655:Lymphocyte Count; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000821:virology*
D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015395:Histocompatibility Antigens Class I; C110764:Mamu-A 01 antigen; D019041:L-Selectin