The function of Ag-specific central (TCM) and effector (TEM) memory CD4+ T lymphocytes remains poorly characterized in vivo in humans. Using CD154 as a marker of Ag-specific CD4+ T cells, we studied the differentiation of memory subsets following anti-hepatitis B immunization. Hepatitis B surface Ag (HBs)-specific memory CD4+ T cells were heterogeneous and included TCM (CCR7+CD27+) and TEM (CCR7−CD27+/−). HBs-specific TCM and TEM shared the capacity to produce multiple cytokines, including IL-2 and IFN-γ. Several years postimmunization, ∼10% of HBs-specific memory CD4+ T cells were in cycle (Ki67+) and the proliferating cells were CCR7+. These results suggest that the model of functional specialization of TCM and TEM cannot be applied to protein vaccine Ags and support the concept that TCM are capable of self-renewal and contribute to maintain the pool of memory cells.
Background: The choice of tetanus prophylaxis for patients with wounds depends on obtaining their vaccination history, which has been demonstrated to be unreliable. Use of a rapid immunoassay (Tétanos Quick Stick, the TQS), combined with knowledge of certain demographic characteristics, may improve the evaluation of tetanus immunity and thus help to avoid inadequate prophylactic measures and reduce costs. Objectives: To evaluate the contribution of the TQS in the choice of tetanus prophylaxis and to perform a costeffectiveness analysis. The final aim was to define the place of the TQS in a modified algorithm for assessment of tetanus immunity in the emergency department. Method: In this Belgian prospective, double-blind, multicentre study, 611 adult patients with a wound were included; 498 (81.5%) records were valid. The TQS test was performed by a nurse before the vaccination history was taken and the choice of prophylaxis was made, using the official algorithm (Belgian Superior Health Council), by a doctor who was unaware of the TQS result. Results: The prevalence of protective anti-tetanus immunity was 74.1%. Immunity was lower in older patients and in female patients. The TQS was a cost-effective tool for patients presenting with a tetanus-prone wound and considered from the vaccination history to be unprotected. Use of the TQS would have improved management in 56.9% (95% CI 47.7% to 65.7%) of patients by avoiding unnecessary treatments, leading to a reduction in the mean cost per patient (J10.58/patient with the TQS versus J11.34/patient without). The benefits of the TQS use were significantly greater in patients ,61 years old: unnecessary treatment would have been avoided in 76.9% (95% CI 65.8% to 85.4%) of cases and the mean cost per patient reduced to J8.31. Conclusion: In selected patients, the TQS is a cost-effective tool to evaluate tetanus immunity. An algorithm is proposed for ED assessment of tetanus immunity integrating age and the TQS result.
Lack of protective immunity against tetanus is frequent but poorly evaluated by history taking. Several demographic characteristics are good predictors of seroprotection. TQS could be a valuable tool in selected patients to improve tetanus prophylaxis in the emergency department.
CCR7+ central memory (T CM ) CD4 + T cells play a central role in long-term immunological memory. Recent reports indicate that a proportion of CD4 + T CM is able to produce effector cytokines. The phenotype and the role of this subset remain unknown. We characterized cytokine-producing human CD4 + T CM specific for cleared protein and persistent viral Ag. Our results demonstrate that the type of Ag stimulation is a major determinant of CD4 + T CM differentiation. CMV-specific T CM were significantly more differentiated than protein Ag-specific T CM and included higher proportions of IFN-c-producing cells. The expression of killer cell lectin-like receptor G1 (KLRG1) by protein Ag-and CMV-specific T CM was associated with increased production of effector cytokines. KLRG1 + T CM expressed high levels of CD127, suggesting that they can survive long term under the influence of IL-7. The induction of KLRG1 + T CM may therefore represent an important target of vaccination against pathogens controlled by cellular immune responses.See accompanying commentary: http://dx
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