Article

Decreased T-Cell Repertoire Diversity in Sepsis: A Preliminary Study

1 Cellular Immunology Laboratory, Hôpital E Herriot, Lyon, France. 2 Hospices Civils de Lyon, Université Claude Bernard Lyon I, Lyon, France. 3 ImmunID Technologies, CEA/iRTSV, Grenoble, France. 4 Hospices Civils de Lyon, Intensive Care Units, Lyon-Sud University Hospital, Pierre-Bénite, Grenoble, France. 5 ImmunID Technologies, CEA/iRTSV, Grenoble, France.
Critical care medicine (Impact Factor: 6.15). 12/2012; 41(1). DOI: 10.1097/CCM.0b013e3182657948
Source: PubMed

ABSTRACT OBJECTIVE:: Septic syndromes are the leading causes of mortality in intensive care units. In patients, the occurrence of sepsis-induced immune suppression is associated with delayed mortality, although the exact role of lymphocyte dysfunctions is not well established. The objective of this study was to investigate T-cell receptor diversity, an important feature of T-cell response, in patients with septic shock. DESIGN:: Preliminary prospective observational study. SETTING:: Adult intensive care units in a university hospital. SUBJECTS:: Patients with septic shock (n = 41) sampled twice after the onset of shock (early after inclusion [day 1] and at the end of the first week [day 7]). MEASUREMENTS AND MAIN RESULTS:: Using a novel molecular biology technique, the combinatorial diversity of human T-cell receptor β-chain (TRB locus) was measured in peripheral blood. Patients with septic shock presented with a marked decreased T-cell receptor diversity after the onset of shock in comparison with normal values. Importantly, in paired samples, a very steep recovery slope of T-cell receptor diversity, never described in other clinical situations, was observed between day 1 and day 7 (p < 0.0001, Wilcoxon's paired test). Decreased T-cell receptor diversity was associated with mortality (log-rank test, p = 0.0058; hazard ratio = 4.48; 95% confidence interval 1.96-53.32), and the development of nosocomial infections (p < 0.05, Mann-Whitney U test). CONCLUSION:: Our results show for the first time that septic patients present with a marked decreased T-cell receptor diversity that returned rapidly toward normal values over time. This opens novel cognitive research perspectives that deserve to be investigated in experimental models of sepsis. After confirmation in larger cohorts of these preliminary results, T-cell receptor diversity measurements may become a crucial tool to monitor immune functions in ICU patients.

0 Bookmarks
 · 
130 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to evaluate the efficacy of Mycobacterium w (Mw), an immunomodulator in severe sepsis.
    Journal of Critical Care 08/2014; DOI:10.1016/j.jcrc.2014.08.012 · 2.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Sepsis is a potentially fatal whole-body inflammatory state caused by severe infection, in which a maladaptive, system-wide inflammatory response follows initial attempts to eliminate pathogens, leading to a dangerous and often fatal increase in the permeability of the blood—brain barrier. These changes in the blood—brain barrier might lead to a major symptom of sepsis, sepsis-associated encephalopathy, which manifests as confusion with a rapid decline in cognitive functions, especially memory, or coma. Once presumed to be entirely reversible, research suggests that sepsis-associated encephalopathy could lead to permanent neurocognitive dysfunction and functional impairments, even after the patient has recovered. Sepsis might act as a major inflammatory hit and potentially increase the brain's susceptibility to neurodegenerative disease, further deterioration of cognitive ability, and risk of developing dementia in later life. Key opportunities for neuroprotective interventions and after-care for people who have survived sepsis might be lost because the long-term neurocognitive and functional consequences of sepsis are not fully characterised.
    The Lancet Neurology 06/2014; 13(6):630-636. DOI:10.1016/S1474-4422(14)70017-1 · 21.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Patients surviving the acute stages of sepsis develop compromised T cell immunity and increased susceptibility to infection. Little is known about the decreased CD4 T cell function after sepsis. We tracked the loss and recovery of endogenous Ag-specific CD4 T cell populations after cecal ligation and puncture-induced sepsis and analyzed the CD4 T cell response to heterologous infection during or after recovery. We observed that the sepsis-induced early loss of CD4 T cells was followed by thymic-independent numerical recovery in the total CD4 T cell compartment. Despite this numerical recovery, we detected alterations in the composition of naive CD4 T cell precursor pools, with sustained quantitative reductions in some populations. Mice that had experienced sepsis and were then challenged with epitope-bearing, heterologous pathogens demonstrated significantly reduced priming of recovery-impaired Ag-specific CD4 T cell responses, with regard to both magnitude of expansion and functional capacity on a per-cell basis, which also correlated with intrinsic changes in Vβ clonotype heterogeneity. Our results demonstrate that the recovery of CD4 T cells from sepsis-induced lymphopenia is accompanied by alterations to the composition and function of the Ag-specific CD4 T cell repertoire. Copyright © 2015 by The American Association of Immunologists, Inc.