Virus-specific cellular immune correlates of survival in vaccinated monkeys after simian immunodeficiency virus challenge.
Understanding the characteristics of the virus-specific T-lymphocyte response that will confer optimal protection against the clinical progression of AIDS will inform the development of an effective cellular immunity-based human immunodeficiency virus vaccine. We have recently shown that survival in plasmid DNA-primed/recombinant adenovirus-boosted rhesus monkeys that are challenged with the simian immunodeficiency virus SIVmac251 is associated with the preservation postchallenge of central memory CD4(+) T lymphocytes and robust gamma interferon (IFN-gamma)-producing SIV-specific CD8(+) and CD4(+) T-lymphocyte responses. The present studies were initiated to extend these observations to determine which virus-specific T-lymphocyte subpopulations play a primary role in controlling disease progression and to characterize the functional repertoire of these cells. We show that the preservation of the SIV-specific central memory CD8(+) T-lymphocyte population and a linked SIV-specific CD4(+) T-lymphocyte response are associated with prolonged survival in vaccinated monkeys following challenge. Furthermore, we demonstrate that SIV-specific IFN-gamma-, tumor necrosis factor alpha-, and interleukin-2-producing T lymphocytes are all comparably associated with protection against disease progression. These findings underscore the contribution of virus-specific central memory T lymphocytes to controlling clinical progression in vaccinated individuals following a primate immunodeficiency virus infection.
Sun
Yue
Y
Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, RE113, Boston, MA 02215, USA.
Schmitz
Jörn E
JE
Buzby
Adam P
AP
Barker
Brianne R
BR
Rao
Srinivas S
SS
Xu
Ling
L
Yang
Zhi-Yong
ZY
Mascola
John R
JR
Nabel
Gary J
GJ
Letvin
Norman L
NL
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007111:Immunity, Cellular; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D016131:Lymphocyte Subsets / Q000276:immunology*; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000401:mortality; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D013223:Statistics as Topic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma