Microflora reactive IL-10 producing regulatory T cells are present in the colon of IL-2 deficient mice but lack efficacious inhibition of IFN-gamma and TNF-alpha production.

WAIDMANN M; ALLEMAND Y; LEHMANN J; DI GENARO S; BÜCHELER N; HAMANN A; AUTENRIETH IB.

GUT - AN INTERNATIONAL JOURNAL OF GASTROENTEOROLOGY AND HEPATOLOGY

B M J PUBLISHING GROUP

Año: 2002 vol. 50 p. 170 - 179

0017-5749

BACKGROUND: Inflammatory bowel disease in interleukin 2 (IL-2) deficient (IL-2(-/-)) mice is triggered by the intestinal microflora and mediated by CD4(+) T cells. AIMS: To determine the characteristics of microflora specific intestinal T cells, including migration and cytokine production. METHODS: Intestinal T cell populations and cytokine mRNA expression of specific pathogen free (SPF) and germ free (GF) IL-2(-/-) and IL-2(+/+) mice were compared by flow cytometry and reverse transcription-polymerase chain reaction. Cytokine production of intestinal mononuclear cells on stimulation with microflora antigens was assessed by ELISA. In vivo migration of T cells was assessed by adoptive transfer of (51)Cr labelled CD4(+)CD25(-)alpha beta(+) T cells. The ability of intestinal T cell lines to promote colitis was determined by adoptive transfer experiments. RESULTS: SPF IL-2(-/-) mice produced higher interferon gamma (IFN-gamma) and tumour necrosis factor alpha mRNA levels than GF IL-2(-/-) mice, which was accompanied by an increased number of CD4(+)alpha beta T cells in the colon. Tracking of (51)Cr labelled and adoptively transferred T cells revealed an increased MAdCAM-1 dependent but VCAM-1 independent recruitment of these cells into the colon of SPF IL-2(-/-) mice. Colon lamina propria lymphocytes (LPL) from SPF IL-2(-/-) mice showed increased spontaneous IFN-gamma production in vitro. On stimulation with bacterial microflora antigens, intraepithelial lymphocytes and LPL did not produce IFN-gamma, but high quantities of IL-10, which did not suppress IFN-gamma production. Bacterial antigen specific cell lines established from colon LPL of SPF IL-2(-/-) mice with colitis showed a regulatory T cell-like cytokine profile and only marginally modulated the course of colitis and survival of IL-2(-/-) mice. CONCLUSIONS: Our results suggest that microflora reactive regulatory T cells are present in the colon of SPF IL-2(-/-) mice. However, IL-10 produced by these cells did not significantly modulate a possible secondary proinflammatory CD4 Th1 cell population to produce IFN-gamma.