NDLI: Emergence of simian immunodeficiency virus-specific cytotoxic CD4+ T cells and increased humoral responses correlate with control of rebounding viremia in CD8-depleted macaques infected with Rev-independent live-attenuated simian immunodeficiency virus.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Von Gegerfelt, Agneta Valentin, Antonio Pavlakis, George N. Alicea, Candido Marthas, Marta L. Montefiori, David C. Van Rompay, Koen K. A. Felber, Barbara K.
Description	Country affiliation: United States Author Affiliation: von Gegerfelt A ( Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA.)
Abstract	Indian rhesus macaques infected with the Rev-independent live-attenuated SIVmac239 strains control viremia to undetectable levels, have persistent but low cellular and humoral anti-SIV responses, and show no signs of immune deficiency. To analyze the immune mechanisms responsible for viral control, five macaques infected at day 1 after birth were subjected to CD8(+) cell depletion at 6.7 y postinfection. This resulted in viremia increases to 3.7-5.5 log(10) RNA copies, supporting a role of CD8-mediated responses in the control of viral replication. The rebounding viremia was rapidly controlled to levels below the threshold of detection, and occurred in the absence of SIV-specific CD8(+) T cells and significant CD8(+) T cell recovery in four of the five animals, suggesting that other mechanisms are involved in the immunological control of viremia. Monitoring immune responses at the time of viral control demonstrated a burst of circulating SIV-specific CD4(+) T cells characterized as CD45RA(-)CD28(+)CD95(+)CCR7(-) and also granzyme B(+), suggesting cytotoxic ability. Control of viremia was also concomitant with increases in humoral responses to Gag and Env, including a transient increase in neutralizing Abs against the neutralization-resistant SIVmac239 in four of five animals. These data demonstrate that a combination of cellular responses mediated by CD4(+) T cells and humoral responses was associated with the rapid control of the rebounding viremia in macaques infected by the Rev-independent live-attenuated SIV, even in the absence of measurable SIV-specific CD8(+) T cells in the blood, emphasizing the importance of different components of the immune response for full control of SIV infection.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	6
Volume Number	185
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2010-09-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antibodies, Viral Biosynthesis Cd4-positive T-lymphocytes Immunology Cd8-positive T-lymphocytes Genes, Env Lymphocyte Depletion Simian Acquired Immunodeficiency Syndrome Prevention & Control Simian Immunodeficiency Virus Up-regulation Viremia Animals Antibodies, Neutralizing Physiology Pathology Virology Cytotoxicity, Immunologic Epitopes, T-lymphocyte Macaca Mulatta Saids Vaccines Administration & Dosage Genetics Vaccines, Attenuated Virus Replication Research Support, N.i.h., Extramural Research Support, N.i.h., Intramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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