B7-H1 is up-regulated in HIV infection and is a novel surrogate marker of disease progression.
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.
Trabattoni
Daria
D
Chair of Immunolgy, Dipartimento Scienze Precliniche Laboratorio Integrato Tecnologie Avanzate (DISP LITA) Vialba, University of Milano, Milano, Italy.
Saresella
Marina
M
Biasin
Mara
M
Boasso
Adriano
A
Piacentini
Luca
L
Ferrante
Pasquale
P
Dong
Haidong
H
Maserati
Renato
R
Shearer
Gene M
GM
Chen
Lieping
L
Clerici
Mario
M
D015703:Antigens, CD; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000494:pharmacology; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000235:genetics; D060890:B7-H1 Antigen; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins; D016022:Case-Control Studies; D018076:DNA, Complementary / Q000097:blood; D018450:Disease Progression; D015658:HIV Infections / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins; D010455:Peptides; D012333:RNA, Messenger / Q000097:blood; D015854:Up-Regulation / Q000187:drug effects
D015703:Antigens, CD; D000998:Antiviral Agents; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D015415:Biomarkers; D001798:Blood Proteins; C423236:CD274 protein, human; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D010455:Peptides; D012333:RNA, Messenger; D016753:Interleukin-10