Decreased T-Cell Repertoire Diversity in Sepsis

Venet, Fabienne; Filipe-Santos, Orchidée; Lepape, Alain; Malcus, Christophe; Poitevin-Later, Françoise; Grivès, Audrey; Plantier, Nadia; Pasqual, Nicolas; Monneret, Guillaume

doi:10.1097/ccm.0b013e3182657948

Cited by 70 publications

(49 citation statements)

References 38 publications

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“…In particular, beside the improvement of T cell viability and functionality, this molecule has been shown to improve TCR repertoire diversifica- tion, whereas septic patients present with a marked decrease in TCR repertoire diversity (21). Similarly, the effect of rhIL-7 involves the downregulation of expression of immunoregulatory receptors such as PD-1, whereas PD-1 expression has been shown to be increased on circulating cells from septic patients (24).…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, far less work has been dedicated to the study of lymphocyte alterations although a link between a reduced delayed-type hypersensitivity response (predominantly mediated by T cells and a hallmark of immune suppression) in ICU patients and increased risk of nosocomial infections and death has been described more than 30 y ago (20). Indeed, sepsis-induced lymphocyte dysfunctions make up 1) a dramatic lymphopenia affecting every lymphocyte subsets associated with major apoptosis, 2) functional alterations such as decreased proliferation and cytokine production in response to stimulation, 3) phenotypic alterations such as increased coinhibitory receptor (CTLA-4 and pro- + Treg (3,21). These lymphocyte dysfunctions are likely illustrated in patients by viral reactivations normally solely occurring in immunocompromised hosts (CMV and herpes simplex virus).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

IL-7 Restores Lymphocyte Functions in Septic Patients

Venet¹,

Foray²,

Villars-Méchin³

et al. 2012

The Journal of Immunology

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176

134

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Septic syndrome is the leading cause of mortality for critically ill patients worldwide. Patients develop lymphocyte dysfunctions associated with increased risk of death and nosocomial infections. In this study, we performed preclinical experiments testing the potential of recombinant human IL-7 (rhIL-7) as a lymphostimulating therapy in sepsis. Circulating IL-7 and soluble IL-7 receptor α-chain (soluble CD127) concentrations were measured in plasma, whereas cellular CD127 expression was evaluated on circulating CD4+ and CD8+ lymphocytes from septic shock patients and healthy volunteers. Lymphocyte proliferation, IFN-γ production, STAT5 phosphorylation, and B cell lymphoma 2 induction were measured ex vivo in response to T cell stimulation in the presence or not of rhIL-7. We show that IL-7 pathway (plasmatic IL-7 concentration and cellular and soluble CD127 expressions) is not overtly altered and remains activable in septic patients. Most importantly ex vivo treatment of patients’ cells with rhIL-7 significantly improves lymphocyte functionality (CD4+ and CD8+ lymphocyte proliferations, IFN-γ production, STAT5 phosphorylation, and B cell lymphoma 2 induction after stimulation). To our knowledge, this constitutes the first report of rhIL-7 ability to restore normal lymphocyte functions in septic patients. These results support the rational for initiating a clinical trial testing rhIL-7 in septic shock.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

IL-7 Restores Lymphocyte Functions in Septic Patients

Venet¹,

Foray²,

Villars-Méchin³

et al. 2012

The Journal of Immunology

Self Cite

176

134

View full text Add to dashboard Cite

show abstract

“…[39][40][41] The function of the remaining T cells is poor in some circumstances, with the degree of T-cell dysfunction predictive of adverse outcomes. [42][43][44] Lymphocytes can also express high levels of negative costimulatory cell surface molecules, such as programmed death (PD)-1, in critical illness. 45,46 These molecules, when ligated, promote apoptosis or cellular deactivation.…”

Section: Treatment-related Factorsmentioning

confidence: 99%

Critical Illness–Induced Immune Suppression: Current State of the Science

Greathouse

Hall

2016

American Journal of Critical Care

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Critical illness comprises a heterogeneous group of serious medical conditions that typically involve an initial proinflammatory process. A compensatory anti-inflammatory response may occur that, if severe and persistent, places the patient at high risk for adverse outcomes including secondary infection and death. Monitoring strategies can identify these patients through measurement of innate and adaptive immune function. Reductions in monocyte HLA-DR expression, reduced cytokine production capacity, increased inhibitory cell surface molecule expression, and lymphopenia have all been associated with this immunesuppressed state. Intriguing data suggest that critical illness-induced immune suppression may be reversible with agents such as interferon-γ, granulocyte macrophage colony-stimulating factor, interleukin 7, or anti-programmed death-1 therapy. Future approaches for characterization of patient-specific immune derangements and individualized treatment could revolutionize how we recognize and prevent complications in critically ill patients.

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“…Although the innate immune system is often generally activated in sepsis, the adaptive immune system is more often in a state of marked immune suppression, characterized by a variety of alterations including a genetically determined, differential regulation of specific host responses (8), a "reprogramming" of leukocytes in response to endotoxin challenge (9), and diminished diversity of T-cell receptors (10). These and other changes modulate the immune response in sepsis (11).…”

Section: Sepsis and Scientific Revolutionsmentioning

confidence: 99%