title: Elevated mucosal addressin cell adhesion molecule-1 expression in acquired immunodeficiency syndrome is maintained during antiretroviral therapy by intestinal pathogens and coincides with increased duodenal CD4 T cell densities.
abstract: Reduced intestinal CD4 T cell numbers and gastrointestinal disease are common features of acquired immunodeficiency syndrome (AIDS). Duodenal lymphocyte densities and mucosal addressin cell adhesion molecule (MAdCAM)-1 expression were analyzed in patients with AIDS after highly active antiretroviral therapy (HAART). Compared with human immunodeficiency virus (HIV)-seronegative individuals, HAART-naive patients with AIDS displayed reduced duodenal CD4 T cell densities. After HAART, AIDS patients with opportunistic intestinal pathogens displayed greater increases in duodenal lamina propria (LP) CD4 T cell densities than patients without such infections. Duodenal MAdCAM-1 expression was elevated in all HAART-naive patients with AIDS but remained elevated only in the intestinal pathogen group after HAART. The data suggest that, in HIV-1 infection, lymphocyte migration to the intestine may be promoted by increased MAdCAM-1 expression. After HAART, opportunistic intestinal pathogens maintain elevated MAdCAM-1 expression, which results in prominent increases in LP CD4 T cell densities in the absence of HIV-mediated CD4 T cell destruction.
authors.affiliation: HIV/GUM Directorate, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, United Kingdom. y.miao@ic.ac.uk
authors.forename: Yin M
authors.initials: YM
authors.lastname: Miao
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hayes
authors.forename: Frances M
authors.initials: FM
authors.lastname: Gotch
authors.forename: Mike C
authors.initials: MC
authors.lastname: Barrett
authors.forename: Nick D
authors.initials: ND
authors.lastname: Francis
authors.forename: Brian G
authors.initials: BG
authors.lastname: Gazzard
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015815:Cell Adhesion Molecules; D004386:Duodenum / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis*; D007150:Immunohistochemistry; D007422:Intestines / Q000382:microbiology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009088:Mucoproteins / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000276:immunology; D019562:Viral Load
chemical_list: D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C504265:MADCAM1 protein, human; D009088:Mucoproteins