Acute HIV infection induces mucosal infiltration with CD4+ and CD8+ T cells, epithelial apoptosis, and a mucosal barrier defect.
OBJECTIVE
A barrier defect of the intestinal mucosa is thought to affect the progression of human immunodeficiency virus (HIV) infection. It is not clear whether the mucosal barrier impairment already is present in acute infection and what mechanisms cause this defect. We analyzed T-cell subsets, epithelial apoptosis, and barrier function of the duodenal mucosa in patients with acute HIV infection.


METHODS
Mucosal T-cell subsets, epithelial apoptosis, and barrier function were assessed by immunohistochemistry, immunofluorescence, flow cytometry, and impedance spectroscopy in duodenal samples from 8 patients with early acute infection, 8 patients with chronic infection, and 9 HIV-negative individuals (controls). One patient was analyzed serially, before and during acute infection.


RESULTS
Compared with controls, densities of mucosal CD8+ and, surprisingly, of mucosal CD4+ T cells too, increased in patients with acute infection. Most mucosal CD4+ T cells had an activated effector memory phenotype (CD45RA-CD45RO+CD62L-CD40L+CD38+) and did not proliferate. Perforin-expressing mucosal CD8+ T cells also were increased in acutely infected patients; their frequency correlated with epithelial apoptosis. The epithelial barrier was impaired significantly in patients with acute HIV infection. The patient analyzed serially developed increased densities of mucosal CD4+ and CD8+ T cells, increased apoptosis of epithelial cells, and mucosal barrier impairment during acute infection.


CONCLUSIONS
Before depleting CD4+ T cells, acute HIV infection induces infiltration of the mucosa with activated effector memory CD4+ and CD8+ T cells. The HIV-induced barrier defect of the intestinal mucosa is evident already in acute infection; it might arise from increased epithelial apoptosis, induced by perforin-positive mucosal cytotoxic T cells.
Epple
Hans-Jörg
HJ
Medical Clinic I, Gastroenterology, Rheumatology, Infectiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin, Germany. hans-joerg.epple@charite.de
Allers
Kristina
K
Tröger
Hanno
H
Kühl
Anja
A
Erben
Ulrike
U
Fromm
Michael
M
Zeitz
Martin
M
Loddenkemper
Christoph
C
Schulzke
Jörg-Dieter
JD
Schneider
Thomas
T
D000208:Acute Disease; D000328:Adult; D000368:Aged; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D004386:Duodenum / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D054353:Perforin / Q000032:analysis
D054353:Perforin