@article{schultz_veltkamp_dieleman_grenther_wyrick_tonkonogy_sartor_2002, title={Lactobacillus plantarum 299V in the treatment and prevention of spontaneous colitis in interleukin-10-deficient mice}, volume={8}, ISSN={["1536-4844"]}, DOI={10.1097/00054725-200203000-00001}, abstractNote={Interleukin (IL)-10-deficient (IL-10−/−) mice develop colitis under specific pathogen-free (SPF) conditions and remain disease free if kept sterile (germ free [GF]). We used four different protocols that varied the time-points of oral administration of Lactobacillus plantarum 299v (L. plantarum) relative to colonization with SPF bacteria to determine whether L. plantarum could prevent and treat colitis induced by SPF bacteria in IL-10−/− mice and evaluated the effect of this probiotic organism on mucosal immune activation. Assessment of colitis included blinded histologic scores, measurements of secreted colonic immunoglobulin isotypes, IL-12 (p40 subunit), and interferon (IFN)-&ggr; production by anti-CD3-stimulated mesenteric lymph node cells. Treating SPF IL-10−/− mice with L. plantarum attenuated previously established colonic inflammation as manifested by decreased mucosal IL-12, IFN-&ggr;, and immunoglobulin G2a levels. Colonizing GF animals with L. plantarum and SPF flora simultaneously had no protective effects. Gnotobiotic IL-10−/− mice monoassociated with L. plantarum exhibited mild immune system activation but no colitis. Pretreatment of GF mice by colonization with L. plantarum, then exposure to SPF flora and continued probiotic therapy significantly decreased histologic colitis scores. These results demonstrate that L. plantarum can attenuate immune-mediated colitis and suggest a potential therapeutic role for this agent in clinical inflammatory bowel diseases.}, number={2}, journal={INFLAMMATORY BOWEL DISEASES}, author={Schultz, M and Veltkamp, C and Dieleman, LA and Grenther, WB and Wyrick, PB and Tonkonogy, SL and Sartor, RB}, year={2002}, month={Mar}, pages={71–80} }
 @article{veltkamp_tonkonogy_de jong_albright_grenther_balish_terhorst_sartor_2001, title={Continuous stimulation by normal luminal bacteria is essential for the development and perpetuation of colitis in Tg is an element of 26 mice}, volume={120}, ISSN={["1528-0012"]}, DOI={10.1053/gast.2001.22547}, abstractNote={BACKGROUND & AIMS
Normal resident bacteria are required for development of colitis in several rodent models. We determined whether bacterial stimulation is necessary for both induction and perpetuation of mucosal inflammation and T-cell activation in Tg(epsilon26) mice, in which transplantation of wild-type bone marrow (BM-->Tg(epsilon26)) causes colitis under specific pathogen-free (SPF) conditions.


METHODS
BM from (C57BL/6 X CBA/J) F1 mice was transplanted into germfree (GF) or SPF Tg(epsilon26) mice. Mesenteric lymph node (MLN) cells from these mice were then transferred into SPF or GF recipients. Colitis and activation of MLN cells were measured by histologic scores, membrane marker analysis, and intracellular cytokine staining. Cytokine secretion by MLN cells stimulated by anti-CD3 or by luminal or epithelial antigens was measured by ELISA.


RESULTS
Colitis did not develop when BM was transferred into GF recipient mice (BM-->GF Tg(epsilon26)). T lymphocytes that secreted interferon gamma upon activation were present in the MLN of BM-->GF Tg(epsilon26) mice, albeit in lower frequency than in control BM-->SPF Tg(epsilon26) mice. Furthermore, transfer of MLN cells from BM-->SPF Tg(epsilon26) mice into SPF Tg(epsilon26) recipients induced active colitis, but not if the same cells were transferred into GF Tg(epsilon26) recipients. Although CD4 T cells were detected in the colonic mucosa of GF recipients, no inflammation was observed for at least 31 weeks. In a reciprocal experiment, MLN cells from BM-->GF Tg(epsilon26) mice without colitis transferred disease to SPF Tg(epsilon26) recipients within 2-4 weeks.


CONCLUSIONS
Activated T cells are present in the mucosa of BM-->GF Tg(epsilon26) mice but are incapable of inducing disease unless colonic bacteria are present. Moreover, pathogenic T cells require the continuous presence of colonic bacteria to sustain colitis.}, number={4}, journal={GASTROENTEROLOGY}, author={Veltkamp, C and Tonkonogy, SL and De Jong, YP and Albright, C and Grenther, WB and Balish, E and Terhorst, C and Sartor, RB}, year={2001}, month={Mar}, pages={900–913} }
 @article{dieleman_arends_tonkonogy_goerres_craft_grenther_sellon_balish_sartor_2000, title={Helicobacter hepaticus does not induce or potentiate colitis in interleukin-10-deficient mice}, volume={68}, ISSN={["1098-5522"]}, DOI={10.1128/IAI.68.9.5107-5113.2000}, abstractNote={ABSTRACT}, number={9}, journal={INFECTION AND IMMUNITY}, author={Dieleman, LA and Arends, A and Tonkonogy, SL and Goerres, MS and Craft, DW and Grenther, W and Sellon, RK and Balish, E and Sartor, RB}, year={2000}, month={Sep}, pages={5107–5113} }
 @article{schultz_tonkonogy_sellon_veltkamp_godfrey_kwon_grenther_balish_horak_sartor_1999, title={IL-2-deficient mice raised under germfree conditions develop delayed mild focal intestinal inflammation}, volume={276}, ISSN={["1522-1547"]}, DOI={10.1152/ajpgi.1999.276.6.g1461}, abstractNote={Interleukin-2 (IL-2) amplifies immune stimuli and influences B cell differentiation. IL-2-deficient mice spontaneously develop intestinal inflammation if raised under specific pathogen-free (SPF) conditions. We quantitatively determined the aggressiveness and kinetics of gastrointestinal and hepatic inflammation in the presence or absence of viable bacteria in IL-2-deficient mice. Breeding colonies were maintained under SPF and germfree (GF) conditions. Intestinal tissues, serum, and mesenteric lymph nodes were obtained from mice at different ages for blind histological scoring, immunoglobulin measurements, mucosal T cell infiltration, and cytokine secretion. GF IL-2 −/− mice developed mild, focal, and nonlethal intestinal inflammation with delayed onset, whereas the more aggressive inflammation in SPF IL-2 −/− mice led to their death between 28 and 32 wk. Periportal hepatic inflammation was equal in the presence or absence of bacterial colonization. Intestinal immunoglobulin secretion decreased significantly by 13 wk of age in IL-2 −/− mice in both GF and SPF environments. In contrast to other genetically engineered rodents, IL-2 −/− mice develop mild focal gastrointestinal and active portal tract inflammation in the absence of viable bacteria.}, number={6}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY}, author={Schultz, M and Tonkonogy, SL and Sellon, RK and Veltkamp, C and Godfrey, VL and Kwon, J and Grenther, WB and Balish, E and Horak, I and Sartor, RB}, year={1999}, month={Jun}, pages={G1461–G1472} }