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Inhibition of CD1d activation suppresses septic mortality: a role for NK-T cells in septic immune dysfunction1 <FN ID="FN1"><NO>1</NO>This paper was presented at the 35th annual meeting of the Association for Academic Surgery, November 9, 2002, Boston, MA.</FN>
- Source :
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Journal of Surgical Research . Nov2003, Vol. 115 Issue 1, p74. 8p. - Publication Year :
- 2003
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Abstract
- Background.Studies indicate that following septic insult there is development of generalized immune dysfunction in T cells, B cells and phagocytes, which is thought to contribute to morbidity and mortality. Specifically, there is a shift in the lymphocytes of septic animals toward an increased release of Th2 cytokines. NK-T cells have been shown to contribute to propagation of the Th2 response. The influence of NK-T cells on the immune response to septic challenge is poorly understood. In this study, we examine whether NK-T cells contribute to the immune dysfunction seen following the onset of polymicrobial sepsis, as produced by cecal ligation and puncture (CLP).Materials and methods.Male 129S1/SvImJ mice were pretreated with either rat IgG (isotypic control) or monoclonal antibody to CD1d (clone 1B1) (0.5 mg), which blocks signaling/antigen presentation via the CD1d cell surface receptor, thereby, ablating the activation and differentiation of the NK-T cells. Septic survival with and without anti-CD1d (CLP/CD1d) pretreatment was assessed. Mice sacrificed 24 h after CLP were assessed for change in splenic %NK-T cell (via flourescense activated cell sector) and for splenic, hepatic, and lymphoid/macrophage production of pro-inflammatory or anti-inflammatory cytokines (via enzyme-linked immunosorbent assay).Results.Administration of anti-CD1d reduced septic mortality 35% at 6–10 d (n = 23 mice/group) (P < .05). There was a consistent increase in the %CD3+ NK1.1+ cell population (NK-T cells) in septic mice (1.706%), which was markedly suppressed by pretreatment with anti-CD1d (0.592%). IL-6 and IL-10 levels were suppressed by anti-CD1d in the spleen and blood.Conclusions.Together these findings imply not only that NK-T cells may play a role in mediating the immune suppression seen in bacterial sepsis, but that inhibition of their activation promotes survival to septic challenge. [Copyright &y& Elsevier]
- Subjects :
- *IMMUNOLOGIC diseases
*T cells
*B cells
*PHAGOCYTES
Subjects
Details
- Language :
- English
- ISSN :
- 00224804
- Volume :
- 115
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Surgical Research
- Publication Type :
- Academic Journal
- Accession number :
- 11098685
- Full Text :
- https://doi.org/10.1016/S0022-4804(03)00220-8