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This information is current as Responses to Infection T Cell + Contributes to Impaired CD 8 T Cell Precursors after Sepsis + CD 8 Sustained and Incomplete Recovery of Naive
| Content Provider | Semantic Scholar |
|---|---|
| Author | Condotta, Stephanie A. Rai, Deepa James, Britnie R. Griffith, Thomas S. Badovinac, Vladimir P. |
| Copyright Year | 2013 |
| Abstract | Patients who survive severe sepsis often display compromised immune function with impairment in innate and adaptive immune responses. These septic patients are highly susceptible to " secondary " infections with intracellular pathogens that are usually controlled by CD8 + T cells. It is not known when and if this observed immunoparalysis of CD8 + T cell immunity recovers, and the long-term consequences of sepsis on the ability of naive CD8 + T cells to respond to subsequent infections are poorly understood. In this study, using the cecal-ligation and puncture mouse model of sepsis, we show that sepsis induces a rapid loss of naive CD8 + T cells. However, IL-15–dependent numerical recovery is observed a month after initial septic insult. Numerical recovery is accompanied by IL-15–dependent phenotypic changes where a substantial proportion of naive (Ag-inexperienced) CD8 + T cells display a " memory-like " phenotype (CD44 hi /CD11a hi). Importantly, the impairment of naive CD8 + T cells to respond to viral and bacterial infection was sustained for month(s) after sepsis induction. Incomplete recovery of naive CD8 + T cell precursors was observed in septic mice, suggesting that the availability of naive precursors contributes to the sustained impairment in primary CD8 + T cell responses. Thus, sepsis can result in substantial and long-lasting changes in the available CD8 + T cell repertoire affecting the capacity of the host to respond to new infections. S epsis, a systemic inflammatory response to severe infection (1–3), is a major public health problem. It is the leading cause of death in noncoronary intensive care units and is the 11th leading cause of death in the United States (4). The early stages of sepsis are associated with a potentially fatal hyperin-flammatory state mediated by proinflammatory cytokines (characterized by IFN-g, IL-12, and IL-6 production) (5, 6). As sepsis progresses, the immunologic response shifts to a hypoinflamma-tory response, which results in an immunosuppressive state, or " immunoparalysis " (5, 7–9). Septic patients exhibit impaired delayed type hypersensitivity responses and the inability to control infections that would typically be eradicated by normally functioning CD8 + T cells (10–14). Several factors can contribute to the immunosuppressive state observed in sepsis, such as increased leu-kocyte apoptosis, deactivated monocyte function, and lymphocyte anergy (5, 15). However, the impact of sepsis on naive CD8 + T cells and their ability to respond to newly introduced pathogen-derived Ags is currently poorly understood. CD8 + … |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/190/5/1991.full.pdf?with-ds=yes |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/early/2013/01/25/jimmunol.1202379.full.pdf |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/early/2013/01/25/jimmunol.1202379.full.pdf?with-ds=yes |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/190/5/1991.full.pdf |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
