Role of CD8+ and CD4+ T lymphocytes in jejunal mucosal injury during murine giardiasis.
T-cell-mediated pathogenesis has been documented in various idiopathic and microbially induced intestinal disorders. Diffuse microvillous shortening seen in giardiasis is responsible for disaccharidase insufficiencies and malabsorption of electrolytes, nutrients, and water. Other mucosal changes include crypt hyperplasia and increased numbers of intraepithelial lymphocytes (IEL). A recent report using an athymic mouse model of infection showed that these epithelial injuries were dependent on T cells. The aim of the present study was to identify which subset of superior mesenteric lymph node (SMLN) T cells were responsible for mucosal alterations in giardiasis. CD4+ and CD8+ T cells, as well as whole lymphocyte populations, were isolated from SMLN of Giardia muris-infected mice for adoptive transfer. Jejunal segments of recipient mice were assessed for brush border ultrastructure, sucrase activity, crypt/villus ratio, and IEL numbers. Mice that received enriched CD8+ and whole SMLN lymphocytes, but not CD4+ T cells, from infected donors showed diffuse shortening of microvilli, loss of brush border surface area, impaired sucrase activity, and increased crypt/villus ratios compared to respective controls. Transfer of whole SMLN lymphocytes, as well as enriched CD4+ or CD8+ T cells, from infected donors led to increased IEL numbers in the recipient jejunum. The findings indicate that loss of intestinal brush border surface area, reduced disaccharidase activities, and increased crypt/villus ratios in giardiasis are mediated by CD8+ T cells, whereas both CD8+ and CD4+ SMLN T cells regulate the influx of IEL.
Scott
Kevin G-E
KG
Mucosal Inflammation Research Group, Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 1N4, Canada.
Yu
Linda C H
LC
Buret
André G
AG
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004186:Disaccharidases / Q000378:metabolism; D005873:Giardiasis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D007583:Jejunum / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D008643:Mesentery / Q000276:immunology; D051379:Mice; D008854:Microscopy, Electron; D008871:Microvilli / Q000473:pathology; D013393:Sucrase / Q000378:metabolism
D004186:Disaccharidases; D013393:Sucrase