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Frequency and phenotypic characteristics of CD4+CD28null T cells in patients with psoriasis and control individuals

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Author(s):
Xinaida Taligare Vasconcelos Lima
Total Authors: 1
Document type: Doctoral Thesis
Press: Campinas, SP.
Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
Defense date:
Examining board members:
Maria Heloisa de Souza Lima Blotta; José Antônio Sanches Junior; Gil Benard; Paulo Eduardo Neves Ferreira Velho; Andrei Carvalho Sposito
Advisor: Maria Heloisa de Souza Lima Blotta
Abstract

Psoriasis is a chronic inflammatory disease that affects the skin and could be associated with increased frequency of cardiovascular events related to atherosclerosis. A subtype of CD4+ T lymphocytes, which does not express the surface molecule CD28 (CD4+CD28null) and is potentially cytotoxic, has increased frequency in peripheral blood of patients with acute coronary syndromes as well as other chronic inflammatory diseases. The objective of this study was to evaluate the frequency and characteristics of circulating CD4+CD28null T cells in patients with psoriasis and control subjects, attempting to correlate these findings with the carotid intima-media thickness (IMT). A total of 42 patients with psoriasis and 42 controls were included. Peripheral blood mononucleated cells (PBMC) from participants were analyzed through flow cytometry for the frequency of CD4+CD28null T lymphocytes and their expression of cytotoxic granules, homing receptors and inflammatory cytokines. Furthermore, these cells were reevaluated in a subgroup of patients that achieved clinical remission of psoriasis after therapy. The main analysis revealed no difference in the frequency of CD4+CD28null T cells between the two groups. However, there were increased numbers of these cells expressing cytotoxic granules and decreased number expressing the chemokine receptor CXCR3 in ex vivo samples of psoriasis patients. These results were sustained in multivariable analysis. Negative correlation was also observed between number of these cells and psoriasis severity. As expected, certain inflammatory markers, such as C-reactive protein, vascular cell adhesion molecule and E-selectin, were increased in patients with psoriasis. On the other hand, there were no differences in IMT between the groups or correlation with number of circulating CD4+CD28null T cells. Although, in the analyses of nine patients after clinical remission of psoriasis, there was no change in the frequency of CD4+CD28null T lymphocytes, numbers of these cells expressing cytotoxic granules were decreased after treatment. These data suggest that, in addition to the inflammatory environment, presence of cells with cytotoxic capabilities may have a role in the pathogenesis of psoriasis, aside from cardiovascular risk factors. Moreover, it is possible that, albeit not significant, decreased number of circulating CD4+CD28null T cells in psoriasis, in addition to a negative correlation with disease severity, could reflect their recruitment to inflammatory sites, such as skin and joints (AU)

FAPESP's process: 11/08718-2 - Frequency and phenotypic characteristics of CD4+CD28null cells in psoriasis patients and healthy subjects - association with cardiovascular risk factors
Grantee:Xinaida Taligare Vasconcelos Lima
Support Opportunities: Scholarships in Brazil - Doctorate