Cd4+ T-Cell Depletion Is Not Associated With Alterations in Survival, Bacterial Clearance, and Inflammation After Cecal Ligation and Puncture

Abstract

Our recent studies indicate that mice depleted of T cells that bear the alphabeta T-cell receptor (alphabeta T cells) show less inflammation, less physiological dysfunction, and improved survival after cecal ligation and puncture (CLP) compared with control mice. Classic CD4(+) and CD8(+) T cells comprise most of the alphabeta T-cell population. We previously showed that CD8(+) T cells, in conjunction with natural killer (NK) cells, participate in CLP-induced inflammation. However, the contribution of CD4(+) T cells to the early inflammatory response caused by CLP is largely undefined. In the present study, we evaluated CLP-induced mortality, bacterial clearance, and inflammation in mice that were depleted of CD4(+) T cells. Compared with control mice, CD4 knockout mice and wild-type mice treated with anti-CD4 did not show significant differences in survival, cytokine production, and systemic bacterial counts. The combined depletion of CD4(+) T and NK cells resulted in improved survival and decreased cytokine production compared with mice possessing a full lymphocyte complement, especially when CD4(+) T and NK cell-deficient mice were treated with imipenem. These improvements were nearly identical to those observed in mice depleted only of NK cells. These studies show that CD4(+) T cells do not seem to play a critical role in facilitating the early inflammatory response caused by CLP.

CD4+lymphocytes control gut epithelial apoptosis and mediate survival in sepsis

“…The role of CD4 ϩ lymphocytes on sepsis-induced mortality is not entirely clear. Two recent studies examining this issue have come to different conclusions, demonstrating that depletion of this cell type either has no effect (38) or is associated with increased mortality in CLP (39). However, the first study used a model with rapid 100% lethality, and neither examined the intestine, making them difficult to compare to our results.…”

Impaired CD4+ T‐cell proliferation and effector function correlates with repressive histone methylation events in a mouse model of severe sepsis

“…Previously published reports that studied CD4+ T cell responses during sepsis have focused primarily on either the acute phase of septic shock[17, 18, 43] or on dysfunction proximal in time to the initial insult[9, 50-52]. Little is understood about CD4+ T cell dysfunction following severe sepsis and its impact on sepsis-induced immunosuppression in both mice and humans.…”

Mitogen-activated protein kinase phosphatase-1 expression in macrophages is controlled by lymphocytes during macrophage activation

“…The viewpoints on the control of innate immune cells by the adaptive immune system during sepsis remain controversial (14)(15)(16)(17)(18). Research using mouse models of sepsis induced by cecal ligation and puncture (CLP) (19) produced different conclusions.…”

“…Research using mouse models of sepsis induced by cecal ligation and puncture (CLP) (19) produced different conclusions. Enoh et al (15) showed that CD4 + T-cell depletion is not associated with alternations in survival, bacterial clearance and inflammation of mice with CLP-induced sepsis. Reim et al (17) showed that T cells contribute both to activation of innate immune cells and to amplification of the immune response against invading pathogens in mice with CLP-induced sepsis, and other septic models have yielded different viewpoints.…”