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Modulation of the immune response in DO11.10 mice by adoptive transfer of differentiated dendritic cells in vitro

Grant number: 05/03507-2
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): January 01, 2006
Effective date (End): December 31, 2008
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Wirla Maria da Silva Cunha Tamashiro
Grantee:Patricia Ucelli Simioni
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil


Immune response in gastrointestinal trait usually results in pathogen elimination. However, dietary proteins as well as comensal microrganisms are tolerated antigens. Tolerance acquired by ingestion of proteins seems to depend on the generation of regulatory or supressor T cells, but dendritic cells (DCs) might be deeply involved in this process. Cytokines from Th1 or Th2 cells may influence DCs to express iNOS or arginase enzymes and thus generate a redox microambient in immunological synapses that interfere with antigen presentation to T lymphocytes. DO11.10 mice, a TCR-OVA specific lineage, has been used to investigate central and peripheral tolerance. Several authors have shown data indicating that DO11.10 mice are susceptible to oral tolerance. However, data from our lab indicate that these transgenic mice produce high levels of specific antibodies following OVA ingestion or peritoneal administration. Differently from BALB/c cells, DCs from transgenic mice immunised by oral route or i.p. are able to stimulate in vitro antigen specific-T cell proliferation. Besides, adoptive transfer of spleen cells from naive BALLB/c mice was enough to break tolerance previously induced in BALB/c mice and improve humoral immune response in DO11.10 mice. In the present work, we shall analyse the effects of adoptive transfer of in vitro differentiated DCs modulated with cytokines (IL-10, TGF-beta, TNF-alpha), LPS or L-arginine inhibitors (N-nitro-L-arginina metil ester, L-NAME e; N-hidroxi-L-arginina, NOHA) on immune response of BALB/c and DO11.10 mice immunised with OVA by oral route or i.p. administration. DCs characterised by flow citometry will be transfered after or before oral treatment of mice with OVA. A subgroup of those mice will be i.p. challenged with OVA. Antibody levels will be determined by ELISA in animal sera. In vitro T cell proliferation experiments will be carried out with splenic T cell from DC recipient mice. Cytokines (IL2, IL-4, IFN-gama e TGF-beta) released in T cell culture supernatants will be measured by ELISA.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SIMIONI, P. U.; FERNANDES, L. G. R.; GABRIEL, D. L.; TAMASHIRO, W. M. S. C.. Effect of aging and oral tolerance on dendritic cell function. Brazilian Journal of Medical and Biological Research, v. 43, n. 1, p. 68-76, . (05/03507-2)
JUSTO, OSELYS RODRIGUEZ; SIMIONI, PATRICIA UCELLI; GABRIEL, DIRCE LIMA; DA SILVA CUNHA TAMASHIRO, WIRLA MARIA; VIEIRA ROSA, PAULO DE TARSO; MORAES, ANGELA MARIA. Evaluation of in vitro anti-inflammatory effects of crude ginger and rosemary extracts obtained through supercritical CO2 extraction on macrophage and tumor cell line: the influence of vehicle type. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE, v. 15, . (15/21365-2, 05/03507-2, 05/04496-4)

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