CD4+ T cells transfer resistance against Citrobacter rodentium-induced infectious colitis by induction of Th 1 immunity.
Citrobacter rodentium induces an acute, self-limited colitis in mice which is histologically associated with crypt hyperplasia. The infection serves as a model for human infectious colitis induced by enteropathogenic Escherichia coli. We investigated if Balb/c mice, which had spontaneously cleared C. rodentium infection, were protected against re-infection and if resistance against intestinal infection can be systemically transferred using spleen cells. The course of infection was monitored by faecal excretion. Spleen cells, splenic CD3+ and CD4+ cells were transferred from resistant mice to non-infected recipients prior to infection. Cytokine secretion, serum and faecal antibody titres and histological disease severity were assessed. Balb/c mice were resistant against re-infection. The course of infection was shorter in mice receiving primed spleen cells, CD3+ and CD4+ cells. Transfer of CD4+ T cells from resistant mice induced gamma-interferon, interleukin (IL)-2 and IL-17 secretion and suppressed IL-10 secretion. Anti-Citrobacter serum IgG1 and IgG2a enzyme-linked immunosorbent assay OD levels were increased. Faecal IgA secretion was increased while serum IgA was suppressed in recipients of CD4+ cells. Large bowel histology showed protection from colitis in recipients of primed cells as indicated by normal colonic epithelium. In Balb/c mice, C. rodentium infection is followed by resistance, which can be transferred by CD4+ cells. Transfer of protection is associated with IL-17 secretion, enhanced serum IgG and faecal IgA secretion. This is the first study to demonstrate the mechanisms by which systemic resistance from previously C. rodentium-infected mice can be transferred to non-infected animals.
Spahn
T W
TW
Department of Medicine B, Muenster University Hospital, Muenster, Germany. spahn@uni-muenster.de
Ross
M
M
von Eiff
C
C
Maaser
C
C
Spieker
T
T
Kannengiesser
K
K
Domschke
W
W
Kucharzik
T
T
D019264:Adoptive Transfer; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D044082:Citrobacter rodentium / Q000276:immunology; D003092:Colitis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D004756:Enterobacteriaceae Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005434:Flow Cytometry; D007070:Immunoglobulin A / Q000032:analysis / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000276:immunology*
D000907:Antibodies, Bacterial; D007070:Immunoglobulin A; D020381:Interleukin-17; D007376:Interleukin-2; D016753:Interleukin-10; D007371:Interferon-gamma