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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2012.tde-10092012-160323
Document
Author
Full name
Fábio Eudes Leal
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Kallas, Esper Georges (President)
Araujo, Adele Caterino de
Benard, Gil
Carvalho Filho, Edgar Marcelino
Marie, Suely Kazue Nagahashi
Title in Portuguese
Alterações de subpopulações de células T CD4+ em indivíduos infectados pelo HTLV-1 com paraparesia espástica tropical (HAM/TSP)
Keywords in Portuguese
Interleucina-17
Linfócitos T CD4-positivos
Paraparesia espástica tropical
Vírus linfotrópico de células T humanas do tipo 1
Abstract in Portuguese
O equilíbrio entre resposta imune e tolerância resulta da complexa interação entre células efetoras e reguladoras. Células capazes de amplificar a resposta imune foram descritas, mas um subgrupo de células T com esta capacidade ainda não foi identificado. Demonstramos que a ectoenzima CD39 ajuda a definir um subgrupo de células T CD4+ denominadas células T indutoras (Tind), capazes de amplificar proliferação e produção de citocinas por células T CD4+ efetoras, antagonizando a atividade supressora de células T reguladoras (Treg). Em doenças auto-imunes e infecções crônicas como a mielopatia associada à infecção pelo HTLV-1 (HAM/TSP), Tinds podem ter papel importante no processo inflamatório exacerbado visto nestas condições clínicas. Demonstramos ainda que as frequências de Treg estão aumentadas em pacientes infectados pelo HTLV-1 independentemente da condição clínica, mas apenas pacientes HAM/TSP apresentam aumento da frequência de Tind. Além disso, a frequência de Tind está associada à carga proviral, considerado fator de risco para o desenvolvimento da HAM/TSP. O aumento da produção de IFN- e a reduzida produção de IL-17 em pacientes HAM/TSP sugerem que células Th17 não possuem papel importante no processo inflamatório relacionado à infecção pelo HTLV-1, diferentemente do que ocorre em condições auto-imunes com quadros clínicos semelhantes à HAM/TSP. Estes dados demonstram importantes alterações no balanço entre inflamação e supressão e sugerem um papel para Tind na patogênese da HAM/TSP
Title in English
CD4+ T cell subsets changes in HTLV-1-infected subjects with tropical spastic paraparesis (HAM/TSP)
Keywords in English
CD4-positive T-lymphocytes
Human T-lymphotropic virus 1
Interleukin-17
Paraparesis tropical spastic
Abstract in English
The balance between immunity and tolerance is a result from the interplay between effector and regulatory cells. An immunoregulatory cell that amplifies cellular immune responses upon activation is already known; however no T-cell subset with such function has been described. We report that the ectoenzyme CD39 helps to delineate a novel subpopulation called inducer T-cell (Tind) that significantly increases the proliferation and cytokine production of effector T cells, counterbalancing the suppressive activity of regulatory T cells (Treg). In autoimmune conditions and chronic viral infections, such as HTLV-1 associated myelopathy, Tinds may play an important role in the inflammatory milieu. Here we show that Treg frequency is increased in HTLV-1-infected subjects regardless of their clinical status, but only HAM/TSP patients have increased frequency of Tind. Besides, Tind frequency is associated to HTLV-1 proviral load, a established risk factor for the development of HAM/TSP. Increased IFN- and reduced IL-17 production seen in HAM/TSP patients suggest that Th17 does not play an important role in the proinflammatory milieu related to HTLV-1 infection, unlike autoimmune disorders with clinical features similar to HAM/TSP. Altogether, our data demonstrate important changes in the inflammatory-regulatory balance and suggest a role for Tind in the pathogenesis of HAM/TSP
 
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FabioEudesLeal.pdf (3.57 Mbytes)
Publishing Date
2012-09-11
 
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