Global dysfunction of CD4 T-lymphocyte cytokine expression in simian-human immunodeficiency virus/SIV-infected monkeys is prevented by vaccination.
Human immunodeficiency virus type 1 infection results in a dysfunction of CD4(+) T lymphocytes. The intracellular events contributing to that CD4(+) T-lymphocyte dysfunction remain incompletely elucidated, and it is unclear whether aspects of that dysfunction can be prevented. The present studies were pursued in a rhesus monkey model of AIDS to explore these issues. Loss of the capacity of peripheral blood CD4(+) T lymphocytes to express cytokines was first detected in simian immunodeficiency virus-infected monkeys during the peak of viral replication during primary infection and persisted thereafter. Moreover, infected monkeys with progressive disease had peripheral blood CD4(+) T lymphocytes that expressed significantly less cytokine than infected monkeys that had undetectable viral loads and intact CD4(+) T-lymphocyte counts. Importantly, CD4(+) T lymphocytes from vaccinated monkeys that effectively controlled the replication of a highly pathogenic immunodeficiency virus isolate following a challenge had a preserved functional capacity. These observations suggest that an intact cytokine expression capacity of CD4(+) T lymphocytes is associated with stable clinical status and that effective vaccines can mitigate against CD4(+) T-lymphocyte dysfunction following an AIDS virus infection.
McKay
Paul F
PF
Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Barouch
Dan H
DH
Schmitz
Jörn E
JE
Veazey
Ronald S
RS
Gorgone
Darci A
DA
Lifton
Michelle A
MA
Williams
Kenneth C
KC
Letvin
Norman L
NL
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism*; D015658:HIV Infections / Q000503:physiopathology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000503:physiopathology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology
D016915:AIDS Vaccines; D016207:Cytokines; D018449:SAIDS Vaccines; D019444:Vaccines, DNA