Evidence for dendritic cell-dependent CD4(+) T helper-1 type responses to commensal bacteria in normal human intestinal lamina propria.
Reactivity of lamina propria (LP) T cells to commensal bacteria has been demonstrated in animal models of inflammatory bowel disease (IBD) and in humans with IBD, but few studies have evaluated the function of such cells in normal individuals. LP mononuclear cells (LPMC) were disaggregated from healthy human intestinal tissue and cultured with heat-killed commensal and pathogenic bacteria. CD3(+)CD4(+) IFN-gamma-producing (Th1) cells reactive to commensal bacteria were demonstrated at frequencies ranging from 0.05 to 2.28% in LPMC. Bacteria-specific Th1 responses were inhibited by anti-HLA-DR antibodies and chloroquine exposure, were enriched in LP relative to peripheral blood, and expressed effector memory cell markers. Bacteria-specific CD4(+) T cell proliferation in vitro was dependent on the presence of LP dendritic cells (DCs), which produced pro-inflammatory cytokines upon bacterial exposure. These results suggest that bacteria-reactive DCs and CD4(+) T cells in normal LP have substantial pro-inflammatory potential that is revealed upon disaggregation in vitro.
Howe
Rawleigh
R
Department of Medicine, University of Colorado Denver, Denver, Colorado 80045, USA.
Dillon
Stephanie
S
Rogers
Lisa
L
McCarter
Martin
M
Kelly
Caleb
C
Gonzalez
Ricardo
R
Madinger
Nancy
N
Wilson
Cara C
CC
D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology*; D004755:Enterobacteriaceae / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012015:Reference Standards; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D055815:Young Adult
D000890:Anti-Infective Agents; D007376:Interleukin-2; D007371:Interferon-gamma; D002738:Chloroquine