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Deficiency of gammadelta T lymphocytes contributes to mortality and immunosuppression in sepsis.
| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Chung, Chun-Shiang Watkins, Lara Funches, Antonio Lomas-Neira, Joanne Cioffi, William G. Ayala, Alfred |
| Description | Country affiliation: United States Author Affiliation: Chung CS ( Div. of Surgical Research, Department of Surgery, Brown University, School of Medicine and Rhode Island Hospital, 593 Eddy St., Providence, RI 02903, USA.) |
| Abstract | Studies have indicated that gammadelta T lymphocytes play an important role in the regulation of immune function and the clearance of intracellular pathogens. We have recently reported that intraepithelial lymphocytes (IEL), which are rich in gammadelta T cells, within the small intestine illustrated a significant increase in apoptosis and immune dysfunction in mice subjected to sepsis. However, the contribution of gammadelta T cells to the host response to polymicrobial sepsis remains unclear. In this study, we initially observed that after sepsis induced by cecal ligation and puncture (CLP), there was an increase in small intestinal IEL CD8+gammadelta+ T cells in control gammadelta+/+ mice. Importantly, we subsequently found an increased early mortality in mice lacking gammadelta T cells (gammadelta-/- mice) after sepsis. This was associated with decreases in plasma TNF-alpha, IL-6, and IL-12 levels in gammadelta-/- mice compared with gammadelta+/+ mice after sepsis. In addition, even though in vitro LPS-stimulated peritoneal macrophages showed a reduction in IL-6 and IL-12 release after CLP, these cytokines were less suppressed in macrophages isolated from gammadelta-/- mice. Alternatively, IL-10 release was not different between septic gammadelta+/+ and gammadelta-/- mice. Whereas T helper (Th)1 cytokine release by anti-CD3-stimulated splenocytes was significantly depressed in septic gammadelta+/+ mice, there was no such depression in gammadelta-/- mice. However, gammadelta T cell deficiency had no effect on Th2 cytokine release. These findings suggest that gammadelta T cells may play a critical role in regulating the host immune response and survival to sepsis, in part by alteration of the level of IEL CD8+gammadelta+ T cells and through the development of the Th1 response. |
| File Format | HTM / HTML |
| ISSN | 03636119 |
| e-ISSN | 15221490 |
| Journal | AJP: Regulatory, Integrative and Comparative Physiology |
| Issue Number | 5 |
| Volume Number | 291 |
| Language | English |
| Publisher | American Physiological Society |
| Publisher Date | 2006-11-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Physiology Cd8-positive T-lymphocytes Immunology Pathology Receptors, Antigen, T-cell, Gamma-delta Genetics Sepsis Mortality Animals Physiology Cell Count Cell Death Epithelial Cells Gene Expression Regulation Histocompatibility Antigens Class Ii Immunosuppression Interleukin-10 Blood Interleukin-12 Interleukin-6 Intestine, Small Mice Mice, Inbred C57bl Mice, Knockout Receptors, Antigen, T-cell, Alpha-beta Metabolism Research Support, N.i.h., Extramural |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Physiology (medical) |
