B7-H1 is up-regulated in HIV infection and is a novel surrogate marker of disease progression

• Published in: Blood Vol. 101; no. 7; pp. 2514 - 2520
• Main Authors: Trabattoni, Daria, Saresella, Marina, Biasin, Mara, Boasso, Adriano, Piacentini, Luca, Ferrante, Pasquale, Dong, Haidong, Maserati, Renato, Shearer, Gene M., Chen, Lieping, Clerici, Mario
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.04.2003; The Americain Society of Hematology
• Subjects: Antigens, CD; Antiretroviral Therapy, Highly Active; Antiviral Agents - pharmacology; B7-1 Antigen - biosynthesis; B7-1 Antigen - genetics; B7-H1 Antigen; Biological and medical sciences; Biomarkers - blood; Blood Proteins; Case-Control Studies; Disease Progression; DNA, Complementary - blood; HIV Infections - etiology; HIV Infections - metabolism; HIV Infections - pathology; Human viral diseases; Humans; Infectious diseases; Interleukin-10 - biosynthesis; Interleukin-10 - genetics; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - pathology; Medical sciences; Membrane Glycoproteins; Peptides; RNA, Messenger - blood; Up-Regulation - drug effects; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Human; Immunopathology; Immune response; Pathogenesis; Cytokine; Retroviridae; Biological marker; AIDS; Immune deficiency; Lentivirus; Costimulatory molecule; Infection; Virus; B7-H1 Molecule; Viral disease; Interleukin 10; T-Lymphocyte; B7 molecule; Human immunodeficiency virus
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-10-3065

The ligation of programmed death-ligand 1 (B7-H1) to T cells results in the preferential production of interleukin 10 (IL-10). We investigated if B7-H1 would be up-regulated in HIV infection, a disease characterized by increased IL-10 production, by measuring B7-H1, B7-1 (CD80), and B7-2 (CD86) expression and mRNA in 36 HIV-infected patients and in 22 healthy controls (HCs). Results showed that (1) B7-H1 expression and mRNA are augmented in cells of HIV patients; (2) increased IL-10 production in these patients is largely induced by B7-H1–expressing CD14+cells; (3) an inverse correlation is detected between B7-H1 expression and CD4 counts, whereas the up-regulation of B7-H1 is directly associated with HIV plasma viremia; (4) antiviral therapy results in the parallel down modulation of IL-10 production and B7-H1 expression/synthesis; and (5) B7-H1/CD80 and B7-H1/CD86 mRNA ratios are increased in peripheral blood mononuclear cells (PBMCs) of HIV patients compared with HCs. B7-H1 synthesis and expression are up-regulated in HIV infection, and the degree of dysregulation correlates with the severity of disease. Aberrant antigen presentation by antigen-presenting cells (APCs) that exhibit increased B7-H1 expression and IL-10 production in HIV infection could be responsible for T-lymphocyte unresponsiveness and loss of protective immunity. B7-H1 is a surrogate marker potentially involved in AIDS disease progression.