Lamina propria CD4+ T lymphocytes synergize with murine intestinal epithelial cells to enhance proinflammatory response against an intracellular pathogen.
Acute and lethal ileitis can be elicited in certain strains of inbred mice after oral infection with the intracellular protozoan parasite Toxoplasma gondii. The development of this inflammatory process is dependent upon the induction of a robust Th1 response, including overproduction of IFN-gamma, TNF-alpha, and NO, as has been reported in other experimental models of human inflammatory bowel disease. In this study we have investigated the role of CD4(+) T cells from the lamina propria (LP) in the early inflammatory events after T. gondii infection using isolated and primary cultured intestinal cells from infected mice and immortalized mouse mIC(cl2) intestinal epithelial cells. Primed LP CD4(+) T cells isolated from parasite-infected mice produce substantial quantities of both IFN-gamma and TNF-alpha. IFN-gamma- and TNF-alpha-producing LP CD4(+) T cells synergize with infected mIC(cl2) and enhance the production of several inflammatory chemokines including macrophage-inflammatory protein-2, monocyte chemoattractant protein-1, monocyte chemoattractant protein-3, macrophage-inflammatory protein-1alphabeta, and IFN-gamma-inducible protein-10. Furthermore, primed LP CD4(+) T cells cocultured with infected mIC(cl2) inhibited replication of the parasite in the intestinal epithelial cells. Thus, LP CD4(+) T cells can interact with parasite-infected intestinal epithelial cells and alter the expression of several proinflammatory products that have been associated with the development of intestinal inflammation. The interaction between these two components of the gut mucosal compartment (CD4(+) T cells and enterocytes) may play a role in the immunopathogenesis of this pathogen-driven experimental inflammatory bowel disease model.
Mennechet
Franck J D
FJ
Department of Microbiology, Dartmouth Medical School, Lebanon, NH 03756, USA.
Kasper
Lloyd H
LH
Rachinel
Nicolas
N
Li
Wen
W
Vandewalle
Alain
A
Buzoni-Gatel
Dominique
D
D000208:Acute Disease; D000276:Adjuvants, Immunologic / Q000502:physiology; D000284:Administration, Oral; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D002450:Cell Communication / Q000276:immunology*; D002461:Cell Line, Transformed; D002469:Cell Separation; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D018920:Coculture Techniques; D016207:Cytokines / Q000502:physiology; D005260:Female; D007079:Ileitis / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology*; D007424:Intracellular Fluid / Q000276:immunology* / Q000469:parasitology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000096:biosynthesis; D014122:Toxoplasma / Q000254:growth & development / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D015854:Up-Regulation / Q000276:immunology
D000276:Adjuvants, Immunologic; D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger