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TGFb and IL2 maintain helminth‐induced FOXP3 expression and increase relative FOXP3 levels in murine gut lamina propria CD8 T cells
Author(s) -
Stoyanoff Korynn,
Blum Arthur,
Hang Long,
Setiawan Tommy,
Weinstock Joel V.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.852.15
Subject(s) - foxp3 , heligmosomoides polygyrus , cd8 , interleukin 10 , biology , mesenteric lymph nodes , immunology , cytotoxic t cell , immune system , lamina propria , epithelium , biochemistry , genetics , in vitro
Intro: The immune system limits gut inflammation. H. polygyrus is a murine intestinal helminth. In lamina propria (Lp), H. polygyrus infection up‐regulates a marker of Tregs, FOXP3, in CD8 + T cells and induces Th2 and regulatory cytokines. This study examined if worm‐induced cytokines enhance FOXP3 expression. Method: Reporter mice, which express a FOXP3‐EGFP fusion protein, were infected with H. polygyrus . After 2 wks, Lp mononuclear cells (LPMC) were isolated. Unfractionated LPMC and FACS sorted EGFP + and EGFP − T cells were cultured 48hr with or without various cytokines (IL10, TGFb, IL2, IL4). Cells then were stained for CD8 and Thy1.2 and analyzed for FOXP3 expression with FACS. Controls included cells from littermates without worms. Results: In LPMC from worm‐infected mice, TGFb/IL2 together increased FOXP3 + CD8 + T cell number and degree of expression: 2.23 ± 0.21, p = 0.002, N = 5 fold increase in number, 1.78 ± 0.18, p = 0.0065, N = 3 fold change in degree of expression. Mesenteric lymph node or spleen cells were unaffected. EGFP − LPMC cultured with TGFb/IL2 did not turn +. EGFP + cells cultured alone lose FOXP3. TGFb/IL2 added to these cultures maintained FOXP3 expression. Discussion: H. polygyrus infection abrogates colitis. Lp CD8 + T cells limit gut inflammation. TGFb/IL2, induced in the gut by worms, maintain but do not induce high FOXP3 levels in CD8 + Tregs and may promote regulation. (DK38327, 058755, 034928)