Pathogen-Specific Induction of CD154 Is Impaired in CD4+ T Cells from Human Immunodeficiency Virus–Infected Patients

• Published in: The Journal of infectious diseases Vol. 189; no. 1; pp. 61 - 70
• Main Authors: Subauste, Carlos S., Wessendarp, Matthew, Portilllo, Jose-Andres C., Andrade, Rosa M., Hinds, Linda M., Gomez, Francisco J., Smulian, A. George, Grubbs, Peter A., Haglund, Lisa A.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01-01-2004; University of Chicago Press; Oxford University Press
• Subjects: AIDS-Related Opportunistic Infections - etiology; Animals; Antigens, CD - biosynthesis; Antigens, Differentiation, T-Lymphocyte - biosynthesis; Antigens, Fungal - pharmacology; Antigens, Protozoan - pharmacology; Biological and medical sciences; Candida albicans - immunology; Candida albicans - pathogenicity; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD40 Ligand - biosynthesis; CD40 Ligand - pharmacology; Cells, Cultured; Cytokines; Cytomegalovirus; Fundamental and applied biological sciences. Psychology; HIV; HIV Infections - immunology; HIV/AIDS; Human viral diseases; Humans; Immunity, Cellular; Infectious diseases; Interferon-gamma - biosynthesis; Interleukin-12 - biosynthesis; Lectins, C-Type; Ligands; Medical sciences; Microbiology; Monocytes; Monocytes - drug effects; Monocytes - immunology; Opportunistic behavior; Pathogens; Physiological immunosuppression; Recombinant Proteins - pharmacology; T lymphocytes; Toxoplasma - immunology; Toxoplasma - pathogenicity; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viruses; Infection; Immunopathology; Microbiology; Viral disease; T-Lymphocyte; AIDS; Immune deficiency
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/380510

The pathogenesis of immunodeficiency associated with human immunodeficiency virus (HIV) infection remains incompletely understood. CD154, a molecule that is expressed primarily on activated CD4+ T cells, is pivotal for regulation of cell-mediated and humoral immunity and is crucial for control of many opportunistic infections. We investigated whether CD4+ T cells from HIV-infected patients exhibit defective induction of CD154 in response to opportunistic pathogens. Incubation of purified human CD4+ T cells with monocytes plus antigenic preparations of either Candida albicans cytomegalovirus, or Toxoplasma gondii resulted in induction of CD154. Expression of CD154 in response to these pathogens was impaired in CD4+ T cells from HIV-infected patients. This defect correlated with decreased production of interleukin (IL)–12 and interferon (IFN)–γ in response to T. gondii. Recombinant CD154 partially restored secretion of IL-12 and IFN-γ in response to T. gondii in cells from HIV-infected patients. Together, defective induction of CD154 is likely to contribute to impaired cell-mediated immunity against opportunistic pathogens in HIV-infected patients