Correlating cellular and molecular signatures of mucosal immunity that distinguish HIV controllers from noncontrollers.
HIV "controllers" are persons infected with human immunodeficiency virus, type I (HIV) who maintain long-term control of viremia without antiviral therapy and who usually do not develop the acquired immune deficiency syndrome (AIDS). In this study, we have correlated results from polychromatic flow cytometry and oligonucleotide expression arrays to characterize the mucosal immune responses of these subjects in relation to untreated HIV(+) persons with high viral loads and progressive disease ("noncontrollers"). Paired peripheral blood and rectosigmoid biopsies were analyzed from 9 controllers and 11 noncontrollers. Several cellular immune parameters were found to be concordant between the 2 compartments. Compared with noncontrollers, the mucosal tissues of controllers had similar levels of effector T cells and fewer regulatory T cells (Tregs). Using principal component analysis to correlate immunologic parameters with gene expression profiles, transcripts were identified that accurately distinguished between controllers and noncontrollers. Direct 2-way comparison also revealed genes that are significantly different in their expression between controllers and noncontrollers, all of which had reduced expression in controllers. In addition to providing an approach that integrates flow cytometry datasets with transcriptional profiling analysis, these results underscore the importance of the sustained inflammatory response that attends progressive HIV disease.
Loke
P'ng
P
Department of Medical Parasitology, New York University Langone Medical Center, New York, NY;
Favre
David
D
Hunt
Peter W
PW
Leung
Jacqueline M
JM
Kanwar
Bittoo
B
Martin
Jeffrey N
JN
Deeks
Steven G
SG
McCune
Joseph M
JM
D000328:Adult; D001706:Biopsy; D012809:Colon, Sigmoid / Q000473:pathology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006679:HIV Seropositivity / Q000097:blood / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D018928:Immunity, Mucosal / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D025341:Principal Component Analysis; D012007:Rectum / Q000473:pathology; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction