T-cell activation differentially mediates the host response to sepsis

• Published in: Shock (Augusta, Ga.) Vol. 34; no. 4; p. 377
• Main Authors: Kasten, Kevin R, Tschöp, Johannes, Goetzman, Holly S, England, Lisa G, Dattilo, Jonathan R, Cave, Cindy M, Seitz, Aaron P, Hildeman, David A, Caldwell, Charles C
• Format: Journal Article
• Language: English
• Published: United States 01.10.2010
• Subjects: Animals; Blotting, Western; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - physiology; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; In Vitro Techniques; Interleukin-6 - metabolism; Lymphocyte Activation - immunology; Lymphocyte Activation - physiology; Male; Mice; Mice, Inbred C57BL; Phagocytosis - physiology; Respiratory Burst - physiology; Sepsis - immunology
• ISSN: 1540-0514
• DOI: 10.1097/SHK.0b013e3181dc0845

Survival during sepsis requires both swift control of infectious organisms and tight regulation of the associated inflammatory response. As the role of T cells in sepsis is somewhat controversial, we examined the impact of increasing antigen-dependent activation of CD4 T cells in a murine model of cecal ligation and puncture using T-cell receptor transgenic II (OT-II) mice that are specific for chicken ovalbumin (OVA) in the context of major histocompatibility complex II. Here, we injected OT-II mice with 0, 1, or 100 μg of OVA and demonstrate that increased antigen treatment resulted in increased numbers of activated splenic CD4 T cells. Vehicle-treated, septic OT-II mice had decreased survival, increased bacterial load, and increased levels of IL-6. Interestingly, this decrease in survival was abrogated when OT-II mice were injected with 1 μg OVA, which was correlated with normalized bacterial load and levels of IL-6. However, when OT-II mice were injected with 100 μg OVA, decreased survival was restored but, in contrast to vehicle-treated OT-II mice, had decreased bacterial load and enhanced IL-6 levels. We also observed that neutrophil oxidative burst and phagocytosis were dependent on CD4 T-cell activation. Further, at extreme levels of T-cell activation, intestinal permeability was significantly increased. Altogether, we conclude that too little CD4 T-cell activation produces dysfunctional neutrophils leading to decreased bacteria clearance and survival, whereas too much CD4 T-cell activation produces a neutrophil phenotype that leads to efficient bacterial clearance but with increased tissue damage and mortality.