Abstract
Dendritic cells (DCs) as antigen presenting cells can stimulate naive CD4+ T cells and initiate the primary immune response which controls Th1/Th2 development. It has been suggested that DCs derived from different tissues have distinct properties. We investigated whether DCs from mesenteric lymph nodes (MLN), Peyer's patches (PP) and spleen (SPL) could induce different responses of naive CD4+ T cells to varying doses of antigen by using a co-culture system of DCs and T cells. DCs from each tissue induced IL-4 secretion from naive CD4+T cells in the presence of low dose antigenic peptide, and induced IFN-γ production at high doses of antigen. When purified CD11c+/B220− DCs were used, MLN-derived DCs induced a higher amount of IFN-γ secretion from naive CD4+ T cells, compared with SPL-derived DCs. We could not detect large differences in the expressions of costimulatory molecules on the surface of these two populations of DCs. On the other hand, we found that large amounts of IL-12 were secreted from MLN DCs in an antigen dose-dependent fashion. In conclusion, DCs from SPL, MLN and PP can induce the production of both IL-4 and IFN-γ from naive CD4+ T cells, depending on antigen dose. MLN-derived CD11c+/B220− DCs induce higher IFN-γ production from naive CD4+ T cells than SPL-derived DCs, through efficient IL-12 secretion.
References
Asselin-Paturel C., Boonstra A., Dalod M., Durand I., Yessaad N., Dezutter-Dambuyant C., Vicari A., O 'Garra A., Biron C., Briere F. and Trinchieri G. 2001. Mouse type I IFN-producing cells are immature APCs with plasmacytoid mor-phology. Nat. Immunol. 2: 1144-1150.
Everson M.P., Lemak D.G., McDuffie D.S., Koopman W.J., McGhee J.R. and Beagley K.W. 1998. Dendritic cells from Peyer 's patch and spleen induce different T helper cell responses. J. Interferon. Cytokine Res. 18: 103-115.
Ise W., Totsuka M., Sogawa Y., Ametani A., Hachimura S., Sato T., Kumagai Y., Habu S. and Kaminogawa S. 2002. Naive CD4+T cells exhibit distinct expression patterns of cytokines and cell surface molecules on their primary responses to varying doses of antigen. J. Immunol. 168: 3242-3250.
Iwasaki A. and Kelsall B.L. 1999. Freshly isolated Peyer 's patch,but not spleen,dendritic cells produce interleukin 10 and induce the differentiation of T helper type 2 cells. J. Exp. Med. 190: 229-239.
Maldonado-Lopez R., De Smedt T., Michel P., Godfroid J., Pajak B., Heirman C., Thielemans K., Leo O., Urbain J. and Moser M. 1999. CD8alpha+and CD8alpha subclasses of dendritic cells direct the development of distinct T helper cells in vivo. J. Exp. Med. 189: 587-592.
McRae B.L., Semnani R.T., Hayes M.P. and van Seventer G.A. 1998. Type I IFNs inhibit human dendritic cell IL-12 produc-tion and Th1 cell development. J. Immunol. 160: 4298-4304.
Nakano H., Yanagita M. and Gunn M.D. 2001. CD11c(+)B220(+)Gr-1(+)cells in mouse lymph nodes and spleen display characteristics of plasmacytoid dendritic cells. J. Exp. Med. 194: 1171-1178.
Nguyen L.T., Radhakrishnan S., Ciric B., Tamada K., Shin T., Pardoll D.M., Chen L., Rodriguez M. and Pease L.R. 2002. Cross-linking the B7 family molecule B7-DC directly acti-vates immune functions of dendritic cells. J. Exp. Med. 196: 1393-1398.
Oppmann B., Lesley R., Blom B., Timans J.C., Xu Y., Hunte B., Vega F., Yu N., Wang J. and Singh K.et al. 2000. Novel p19 protein engages IL-12p40 to form a cytokine,IL-23,with biological activities similar as well as distinct from IL-12. Immunity 13: 715-725.
Ranger A.M., Das M.P., Kuchroo V.K. and Glimcher L.H. 1996. B7-2 (CD86)is essential for the development of IL-4-producing T cells. Int. Immunol. 8: 1549-1560.
Rogers P.R. and Croft M. 2000. CD28,Ox-40,LFA-1,and CD4 modulation of Th1/Th2 differentiation is directly dependent on the dose of antigen. J. Immunol. 164: 2955-2963.
Ruedl C., Bachmann M.F. and Kopf M. 2000. The antigen dose determines T helper subset development by regulation of CD40 ligand. Eur. J. Immunol. 30: 2056-2064.
Sato A., Hashiguchi M., Hachimura S. and Kaminogawa S. 2002. Murine Peyer 's patch to produce IFN-c Cytotechnology 40: 31-38.
Sato T., Sasahara T., Nakamura Y., Osaki T., Hasegawa T., Tadakuma T., Arata Y., Kumagai Y., Katsuki M. and Habu S. 1994. Naive T cells can mediate delayed-type hypersensi-tivity response in T cell receptor transgenic mice. Eur. J. Immunol. 24: 1512-1516.
Tseng S.Y., Otsuji M., Gorski K., Huang X., Slansky J.E., Pai S.I., Shalabi A., Shin T., Pardoll D.M. and Tsuchiya H. 2001. B7-DC,a new dendritic cell molecule with potent costimu-latory properties for T cells. J. Exp. Med. 193: 839-846.
Yoshida T., Hachimura S., Ishimori M., Kinugasa F., Ise W., Totsuka M., Ametani A. and Kaminogawa S. 2002. Antigen presentation by Peyer 's patch cells can induce both Th1-and Th2-type responses depending on antigen dosage,but a different cytokine response pattern from that of spleen cells. Biosci. Biotechnol. Biochem. 66: 963-969. 55
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Hibi, M., Hachimura, S., Ise, W. et al. Dendritic Cells from Spleen, Mesenteric Lymph Node and Peyer's Patch Can Induce the Production of Both IL-4 and IFN-γ from Primary Cultures of Naive CD4+ T Cells in a Dose-Dependent Manner. Cytotechnology 43, 49–55 (2003). https://doi.org/10.1023/B:CYTO.0000039906.15156.cd
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DOI: https://doi.org/10.1023/B:CYTO.0000039906.15156.cd