Role of regulatory T cells in long-term immune dysfunction associated with severe sepsis


Autoria(s): NASCIMENTO, Daniele C.; ALVES-FILHO, Jose C.; SONEGO, Fabiane; FUKADA, Sandra Y.; PEREIRA, Marcelo S.; BENJAMIM, Claudia; ZAMBONI, Dario S.; SILVA, Joao S.; CUNHA, Fernando Q.
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

19/10/2012

19/10/2012

2010

Resumo

Objective: To investigate the role of regulatory T cells in the modulation of long-term immune dysfunction during experimental sepsis. It is well established that sepsis predisposes to development of a pronounced immunosuppression. Nevertheless, the mechanisms underlying the immune dysfunction after sepsis are still not well understood. Design: Prospective experimental study. Setting: University research laboratory. Interventions: Wild-type mice underwent cecal ligation and puncture and were treated with antibiotic during 3 days after surgery. On days 1, 7, or 15 after cecal ligation and puncture, the frequency of regulatory T cells, proliferation of CD4(+) T cells and bacterial counts were evaluated. Fifteen days after cecal ligation and puncture, surviving mice underwent secondary pulmonary infection by intranasal inoculation of nonlethal dose of Legionella pneumophila. Some mice received agonistic glucocorticoid-induced tumor necrosis factor receptor antibody (DTA-1) before induction of secondary infection. Measurements and Main Results: Mice surviving cecal ligation and puncture showed a markedly increased frequency of regulatory T cells in thymus and spleen, which was associated with reduced proliferation of CD4(+) T cells. Fifteen days after cecal ligation and puncture, all sepsis-surviving mice succumbed to nonlethal injection of L. pneumophila. Treatment of mice with DTA-1 antibody reduced frequency of regulatory T cells, restored CD4(+) T cell proliferation, reduced the levels of bacteria in spleen, and markedly improved survival of L. pneumophila infection. Conclusion: These findings suggest that regulatory T cells play an important role in the progression and establishment of immune dysfunction observed in experimental sepsis. (Crit Care Med 2010; 38: 1718-1725)

Conselho Nacional de Pesquisa e Desenvolvimento Tecnologico (CNPq) (FDQ, JSS)

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) (FDQ, JSS, DSZ)

Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)

Identificador

CRITICAL CARE MEDICINE, v.38, n.8, p.1718-1725, 2010

0090-3493

http://producao.usp.br/handle/BDPI/24319

10.1097/CCM.0b013e3181e78ad0

http://dx.doi.org/10.1097/CCM.0b013e3181e78ad0

Idioma(s)

eng

Publicador

LIPPINCOTT WILLIAMS & WILKINS

Relação

Critical Care Medicine

Direitos

restrictedAccess

Copyright LIPPINCOTT WILLIAMS & WILKINS

Palavras-Chave #sepsis #immunosuppression #Tregs #GITR family-related gene #LEGIONELLA-PNEUMOPHILA INFECTION #INDUCED TNF RECEPTOR #POLYMICROBIAL SEPSIS #SELF-TOLERANCE #SEPTIC SHOCK #SUPPRESSION #SURVIVAL #SUSCEPTIBILITY #LIGATION #MICE #Critical Care Medicine
Tipo

article

original article

publishedVersion