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Journal of Virology, April 2003, p. 4695-4702, Vol. 77, No. 8
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.8.4695-4702.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Global Dysfunction of CD4 T-Lymphocyte Cytokine Expression in Simian-Human Immunodeficiency Virus/SIV-Infected Monkeys Is Prevented by Vaccination

Paul F. McKay,1 Dan H. Barouch,1 Jörn E. Schmitz,1 Ronald S. Veazey,2 Darci A. Gorgone,1 Michelle A. Lifton,1 Kenneth C. Williams,1 and Norman L. Letvin1*

Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215,1 Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana 704332

Received 7 October 2002/ Accepted 23 January 2003

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.

* Corresponding author. Mailing address: Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215. Phone: (617) 667-2766. Fax: (617) 667-8210. E-mail: nletvin{at}bidmc.harvard.edu.

Journal of Virology, April 2003, p. 4695-4702, Vol. 77, No. 8
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.8.4695-4702.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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