Simian immunodeficiency virus (SIV) infection of a rhesus macaque induces SIV-specific CD8(+) T cells with a defect in effector function that is reversible on extended interleukin-2 incubation.
A vigorous expansion of antigen-specific CD8(+) T cells lacking apparent effector function was observed in a rhesus macaque acutely infected with the simian immunodeficiency virus (SIV) strain SIVmac239. Antigen-specific CD8(+) T cells were identified using antigenic-peptide class I major histocompatibility complex tetramers. As many as 8.3% of CD8(+) cells recognized the Mamu-A*01-associated SIV epitope Gag(181-189) (CTPYDINQM); however, these cells demonstrated no effector function when presented with peptide-incubated targets, as measured by intracellular cytokine staining for gamma interferon (IFN-gamma), interleukin-2 (IL-2) production, or direct cellular lysis. Similar results were observed with three other SIV peptide antigens. Nonresponsiveness did not correlate with apoptosis of the CD8(+) cells, nor were cells from this macaque impaired in their ability to present peptide antigens. Associated with the nonresponsive state was a lack of IL-2 production and decreased IL-2 receptor expression. Exogenous IL-2 treatment for 1 week in the absence of antigenic stimulation restored antigen-specific responses and the quantitative correlation between tetramer recognition and antigen-responsive IFN-gamma secretion. This case report suggests a regulatory mechanism that may impede the effector function of antigen-specific T cells during acute infection with SIV or human immunodeficiency virus in some cases. This mechanism may participate in the failure of the immune system to limit infection.
Department of Medicine, University of Toronto, Ontario, Canada.
Y
Y
Xiong
M A
MA
Luscher
J D
JD
Altman
M
M
Hulsey
H L
HL
Robinson
M
M
Ostrowski
B H
BH
Barber
K S
KS
MacDonald
D000818:Animals; D017951:Antigen Presentation; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology* / Q000378:metabolism; D008253:Macaca mulatta; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma