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| Author(s): |
Eduardo Aleixo Figueira
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Bauru. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Odontologia de Bauru (FOB/SDB) |
| Defense date: | 2007-06-21 |
| Examining board members: |
Ana Paula Campanelli;
Sebastião Luiz Aguiar Greghi;
Ana Paula de Souza Pardo
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| Advisor: | Ana Paula Campanelli |
| Abstract | |
Negative co-stimulatory signals mediated via cell surface molecules such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1) play a critical role in down-modulation immune responses and maintaining peripheral tolerance. Both CTLA-4 and PD-1 are induced on activated T cells, and these are involved in the immunopathogenesis of periodontal diseases. However, there are no reports linking PD-1 with periodontal diseases. We investigated the possible association between CD28, CTLA-4 and PD-1 expression and cytokine production with putative lymphocytes dysfunction in patients with periodontal diseases. Blastogenic response to PHA was no difference between groups. However, blastogenic response to Aa and Pg antigen was increased in gingivitis group. After stimulation with antigens or PHA, IL-10 and IFN- production was induced in vitro by PBMCs from patients with periodontal disease and healthy subjects. The expression of CTLA-4 and PD-1 was higher in blood T cells from patients as compared with the healthy groups. However, blockage of PD-1 did not modify blastogenic response, but resulted in modulation of IFN- and IL-10 production. In situ, we observed a significant increase in the total number of leukocytes from chronic periodontitis lesion as compared with the gingivitis and healthy groups. Additionally, there was no difference in the composition of cellular infiltrate. The results showed that CD3+ T cells represented the main population; in particular, the proportion of CD4+ T cells was significantly higher than CD8+ T cells, in chronic periodontitis groups. The expression of CD28 was similar in both groups studied. On the other hand, the expression of CTLA-4 and PD-1 was significantly higher in T cells from chronic periodontitis groups as compared with the gingivitis group. Importantly, PD-1 expression was observed primarily in CD4+ T cells. Similar amounts of T cells expressing CD28+ and CTLA-4+ were found in gingivitis and chronic periodontitis patients. This study demonstrates the expression of PD-1 and CTLA-4 in T cells of blood and lesions from patients with periodontal diseases and suggests the possible involvement of these molecules on immune regulation of periodontal disease. (AU) | |