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Published online before print July 6, 2005

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(Journal of Leukocyte Biology. 2005;78:772-776.)
© 2005 by Society for Leukocyte Biology

Morphine inhibits CD8⁺ T cell-mediated, noncytolytic, anti-HIV activity in latently infected immune cells

Xu Wang^*, Ning Tan, Steven D. Douglas^*, Ting Zhang^*, Yan-Jian Wang^* and Wen-Zhe Ho^*,1

^* Division of Allergy and Immunology, Joseph Stokes, Jr., Research Institute at The Children’s Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine; and
Department of Medicine, The People’s Hospital of Guangdong Province, Guangzhou, People’s Republic of China

¹Correspondence: Division of Allergy and Immunology, The Children’s Hospital of Philadelphia, 34th Street & Civic Center Boulevard, Philadelphia, PA 19104. E-mail: ho{at}email.chop.edu

Opiates have profound effects on the function of human immune cells and are a possible cofactor in the immunopathogenesis of human immunodeficiency virus (HIV) disease. We investigated the impact of morphine on CD8⁺ T cell-mediated, noncytotoxic, anti-HIV activity in latently infected human immune cells. Morphine inhibited the noncytotoxic, anti-HIV activity of CD8⁺ T cells in HIV latently infected cells (U1 and J1.1). Naltrexone abrogated the morphine-mediated, inhibitory effect on the noncytotoxic, anti-HIV activity of CD8⁺ T cells. Interferon- (IFN-), a potent antiviral cytokine produced by CD8⁺ T cells, was partially responsible for CD8⁺ T cell-mediated, noncytotoxic, anti-HIV activity. The anti-HIV activity of IFN- was also compromised by morphine treatment. Further, morphine attenuated CD8⁺ T cell-mediated suppression of the HIV long-terminal repeat promoter activation. Morphine also inhibited CD8⁺ T cell-induced expression of the signal transducer and activator of transcription-1, an important transcriptional factor in the IFN signaling pathway. These data provide additional evidence to support the notion that opioids play a role in impairing the anti-HIV function of the immune system.

Key Words: IFN- • PBMC • U1 cells • J1.1 cells