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HAM/TSP-DERIVED HTLV-1-INFECTED T CELL LINES PROMOTE MORPHOLOGICAL AND FUNCTIONAL CHANGES IN HUMAN ASTROCYTES CELL LINES: POSSIBLE ROLE IN THE ENHANCED T CELLS RECRUITMENT INTO CENTRAL NERVOUS SYSTEM
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Ministério da Saúde. Instituto Nacional de Saúde. Maputo, Mozambique / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Câncer. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Estrutural. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Câncer. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Estrutural. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Abstract
Background: The mechanisms through which HTLV-1 leads to and maintains damage in the central nervous system of
patients undergoing HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) are still poorly understood. In
recent years, increasing evidence indicates that, not only lymphocytes but also glial cells, in particular astrocytes, play a
role in the pathophysiology of HAM/TSP. In this study we used a model of co-culture between human HTLV-1-infected
(CIB and C91PL) and non-infected (CEM) T lymphocyte cell lines and astrocyte (U251 and U87) cell lines to mimic the
in vivo T cell-astrocyte interactions.
Results: We first observed that CIB and C91PL adhere strongly to cultured astrocytes cell lines, and that co-cultures of
HTLV-1 infected and astrocyte cell lines cells resulted in rapid syncytium formation, accompanied by severe
morphological alterations and increased apoptotic cell death of astrocyte cells. Additionally, cultures of astrocyte cell
lines in presence of supernatants harvested from HTLV-1-infected T cell cultures resulted in significant increase in the
mRNA of CCL2, CXCL1, CXCL2, CXCL3, CXCL10, IL-13, IL-8, NFKB1, TLR4, TNF, MMP8 and VCAM1, as compared with the
values obtained when we applied supernatants of non-infected T- cell lines. Lastly, soluble factors secreted by cultured
astrocytic cell lines primed through 1-h interaction with infected T cell lines, further enhanced migratory responses, as
compared to the effect seen when supernatants from astrocytic cell lines were primed with non-infected T cell lines.
Conclusion: Collectively, our results show that HTLV-1 infected T lymphocyte cell lines interact strongly with astrocyte
cell lines, leading to astrocyte damage and increased secretion of attracting cytokines, which in turn may participate in
the further attraction of HTLV-1-infected T cells into central nervous system (CNS), thus amplifying and prolonging the
immune damage of CNS.
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