This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sinistro, A.
Right arrow Articles by Bergamini, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sinistro, A.
Right arrow Articles by Bergamini, A.

 Previous Article  |  Next Article 

Clinical and Vaccine Immunology, December 2008, p. 1851-1858, Vol. 15, No. 12
1071-412X/08/$08.00+0     doi:10.1128/CVI.00184-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Downregulation of CD40 Ligand Response in Monocytes from Sepsis Patients{triangledown}

Anna Sinistro,1 Cristiana Almerighi,3 Chiara Ciaprini,3 Silvia Natoli,2 Emanuele Sussarello,2 Sara Di Fino,3 Francesca Calò-Carducci,1 Giovanni Rocchi,1 and Alberto Bergamini1*

Department of Public Health and Cellular Biology,1 Intensive Care Unit,2 Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy3

Received 16 May 2008/ Returned for modification 3 July 2008/ Accepted 15 October 2008

It has been suggested that a defective adaptive immune response contributes to septic immunosuppression. Here, the response of monocytes to CD40 ligand (CD40L) for patients with sepsis due to infection with gram-negative organisms has been analyzed. Compared to cells from controls, monocytes from septic patients showed significantly reduced production of tumor necrosis factor alpha, interleukin-1β (IL-1β), and IL-12 and were unable to acquire high levels of CD80 and CD86 molecules. These alterations were observed at the onset of sepsis and persisted at day 7. However, the ability of monocytes to respond to CD40L stimulation was partially but significantly restored in cells from patients who recovered from sepsis. In addition, costimulation of autologous CD4+ T lymphocytes by CD40L-activated monocytes from septic patients failed to induce cell proliferation and gamma interferon production. Finally, the ability of CD40L to rescue monocytes from apoptosis was severely impaired. We conclude that downregulation of the CD40L response may be an appropriate model for the monocyte alteration observed during septic immunosuppression and may help in the development of novel therapeutic strategies.

* Corresponding author. Mailing address: Dipartimento di Sanità Pubblica e Biologia Cellulare, Cattedra di Malattie Infettive, Università di Roma Tor Vergata, Via Montpellier 1, 00173 Roma, Italy. Phone: 39 (335) 5372165. Fax: 39 (06) 2020799. E-mail: bergamini{at}med.uniroma2.it

{triangledown} Published ahead of print on 22 October 2008.

Clinical and Vaccine Immunology, December 2008, p. 1851-1858, Vol. 15, No. 12
1071-412X/08/$08.00+0     doi:10.1128/CVI.00184-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»