The proliferation, differentiation and regulatory function of T cells in the intestinal lamina propria is thought to depend largely on their production of cytokines. Previously we have shown in nonhuman primates that intestinal lamina propria (LPL) T cells have high expression of IL-2 receptors, have high capacity for IL-2 production, and produce helper factors for immunoglobulin synthesis in response to intestinal pathogens. In the present study we investigated the response of nonhuman primate T cells to human recombinant IL-4 and have examined their capacity to produce B cell proliferation factors. T cells from MLN exhibited a dose-dependent proliferative response (3H-thymidine incorporation) when cultured with rIL-4. The response was dependent on the presence of phorbol myristate acetate (PMA) as a co-stimulus. In contrast, LPL T cells had a minimal response to rIL-4, but did not have responses to rIL- 2 and the mitogen concanavalin A. To investigate lymphokine production by T cells, culture supernatants from concanavalin A stimulated T cells were obtained. Using a Staph A Cowans (SAC) co- stimulation assay, it was shown that supernatants from both MLN and LPL T cells stimulate proliferation of MLN B cells. In addition, it was shown that mitogen activated LPL T cells produce substantially higher IFN-gamma bioactivity and have much higher levels of IFN-gamma mRNA than activated MLN T cells. These studies show for the first time that the two major lymphoid compartments of intestinal immune system, organized lymphoid cells in the mesenteric lymph nodes and diffusely scattered lymphocytes in the intestinal lamina propria, are fundamentally different in their production and utilization of the lymphokines IL-2, IL-4 and IFN- gamma.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000432-04
Application #
3818231
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Strober, Warren; Kitani, Atsushi; Fichtner-Feigl, Stefan et al. (2009) The signaling function of the IL-13Ralpha2 receptor in the development of gastrointestinal fibrosis and cancer surveillance. Curr Mol Med 9:740-50
Fichtner-Feigl, Stefan; Fuss, Ivan J; Young, Cheryl A et al. (2007) Induction of IL-13 triggers TGF-beta1-dependent tissue fibrosis in chronic 2,4,6-trinitrobenzene sulfonic acid colitis. J Immunol 178:5859-70
Boirivant, Monica; Strober, Warren (2007) The mechanism of action of probiotics. Curr Opin Gastroenterol 23:679-92
Fuss, Ivan J; Becker, Christoph; Yang, Zhiqiong et al. (2006) Both IL-12p70 and IL-23 are synthesized during active Crohn's disease and are down-regulated by treatment with anti-IL-12 p40 monoclonal antibody. Inflamm Bowel Dis 12:9-15
Strober, Warren; Fuss, Ivan J (2006) Experimental models of mucosal inflammation. Adv Exp Med Biol 579:55-97
Leon, Francisco; Contractor, Nikhat; Fuss, Ivan et al. (2006) Antibodies to complement receptor 3 treat established inflammation in murine models of colitis and a novel model of psoriasiform dermatitis. J Immunol 177:6974-82
Oida, Takatoku; Xu, Lili; Weiner, Howard L et al. (2006) TGF-beta-mediated suppression by CD4+CD25+ T cells is facilitated by CTLA-4 signaling. J Immunol 177:2331-9
Fichtner-Feigl, Stefan; Strober, Warren; Kawakami, Koji et al. (2006) IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta1 production and fibrosis. Nat Med 12:99-106
Strober, Warren (2006) Immunology. Unraveling gut inflammation. Science 313:1052-4
Di Giacinto, Claudia; Marinaro, Mariarosaria; Sanchez, Massimo et al. (2005) Probiotics ameliorate recurrent Th1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-beta-bearing regulatory cells. J Immunol 174:3237-46

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