PMID- 11788555
OWN - NLM
STAT- MEDLINE
DCOM- 20020213
LR  - 20190501
IS  - 0017-5749 (Print)
IS  - 1458-3288 (Electronic)
IS  - 0017-5749 (Linking)
VI  - 50
IP  - 2
DP  - 2002 Feb
TI  - 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.
PG  - 170-9
AB  - 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.
FAU - Waidmann, M
AU  - Waidmann M
AD  - Max von Pettenkofer-Institut fur Hygiene und Medizinische Mikrobiologie, 
      Universitat Munchen, Pettenkofer Strasse 9a, 80336 Munchen, Germany.
FAU - Allemand, Y
AU  - Allemand Y
FAU - Lehmann, J
AU  - Lehmann J
FAU - di Genaro, S
AU  - di Genaro S
FAU - Bucheler, N
AU  - Bucheler N
FAU - Hamann, A
AU  - Hamann A
FAU - Autenrieth, I B
AU  - Autenrieth IB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Gut
JT  - Gut
JID - 2985108R
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Immunoglobulins)
RN  - 0 (Interleukin-2)
RN  - 0 (Madcam1 protein, mouse)
RN  - 0 (Mucoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adoptive Transfer/methods
MH  - Animals
MH  - Antigens, Bacterial/analysis
MH  - Bacteroides/immunology
MH  - CD4-Positive T-Lymphocytes/metabolism/*microbiology
MH  - Cell Adhesion Molecules
MH  - Cell Line
MH  - Cell Movement/physiology
MH  - Colitis/metabolism/microbiology
MH  - Colon/metabolism/*microbiology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Immunoglobulins/physiology
MH  - Interferon-gamma/*antagonists & inhibitors/metabolism
MH  - Interleukin-10/*metabolism
MH  - Interleukin-2/*deficiency
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mucoproteins/physiology
MH  - Polymerase Chain Reaction/methods
MH  - RNA, Messenger/metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
PMC - PMC1773105
EDAT- 2002/01/15 10:00
MHDA- 2002/02/14 10:01
PMCR- 2005/02/01
CRDT- 2002/01/15 10:00
PHST- 2002/01/15 10:00 [pubmed]
PHST- 2002/02/14 10:01 [medline]
PHST- 2002/01/15 10:00 [entrez]
PHST- 2005/02/01 00:00 [pmc-release]
AID - 0500170 [pii]
AID - 10.1136/gut.50.2.170 [doi]
PST - ppublish
SO  - Gut. 2002 Feb;50(2):170-9. doi: 10.1136/gut.50.2.170.