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Prepublished online as a Blood First Edition Paper on December 5, 2002; DOI 10.1182/blood-2002-10-3065.
Submitted October 10, 2002
Accepted November 13, 2002
B7-H1 is Upregulated in HIV infection and is a Novel Surrogate Marker of Disease Progression
Daria Trabattoni, Marina Saresella, Mara Biasin, Adriano Boasso, Luca Piacentini, Pasquale Ferrante, Haidong Dong, Renato Maserati, Gene M Shearer, Lieping Chen, and Mario Clerici*
Immunology, University of Milano, DISP LITA VIALBA, Milano, Italy
Biology, Don C. Gnocchi Foundation, IRCCS, Milano, Italy
Virology, University of Milano, DISP LITA VIALBA, Milano, Italy
Immunology, Mayo Clinic, Rochester, MN, USA
Infectious Diseases, IRCCS San Matteo, Pavia, Italy
EIB, NCI, NIH, Bethesda, MD, USA
* Corresponding author; email: mago{at}mailserver.unimi.it.
The ligation of programmed death-ligand 1 (B7-H1) to T cells results in the preferential production of IL-10. We investigated if B7-H1 would be upregulated 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 (HC). 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 upregulation 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 PBMC of HIV patients compared to HC. B7-H1 synthesis and expression is upregulated in HIV infection and the degree of dysregulation correlates with the severity of disease. Aberrant antigen presentation by APC 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.
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