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Merci Kusel

Publications and source records attributed to Merci Kusel.

3 recordsLinked to original sources

Dendritic cell immaturity during infancy restricts the capacity to express vaccine-specific T-cell memory.

The capacity of the immune system in infants to develop stable T-cell memory in response to vaccination is attenuated, and the mechanism(s) underlying this developmental deficiency in humans is poorly understood. The present study focuses on the capacity for expression of in vitro recall responses to tetanus and diphtheria antigens in lymphocytes from 12-month-old infants vaccinated during the first 6 months of life. We demonstrate that supplementation of infant lymphocytes with "matured" dendritic cells (DC) cultured from autologous CD14+ precursors unmasks previously covert cellular immunity in the form of Th2-skewed cytokine production. Supplementation of adult lymphocytes with comparable prematured autologous DC also boosted vaccine-specific T-cell memory expression, but in contrast to the case for the infants, these cytokine responses were heavily Th1 skewed. Compared to adults, infants had significantly fewer circulating myeloid DC (P < 0.0001) and plasmacytoid DC (P < 0.0001) as a proportion of peripheral blood mononuclear cells. These findings suggest that deficiencies in the numbers of antigen-presenting cells and their functional competence at 12 months of age limit the capacity to express effector memory responses and are potentially a key factor in reduced vaccine responsiveness in infants.

Adult↗

Piloting a web-based continuing professional development program for asthma education.

PURPOSE: Continuing professional development is an integral component of modern medical practice, yet traditional educational methods are impractical for many Primary Care Physicians. Web-based programs may fulfill the requirements of busy practitioners who have difficulty attending formal education sessions. METHODS: We piloted the use of a learning management system to deliver asthma education materials to Primary Care Physicians in both Australia and Italy in their native languages. Each group of Physicians accessed an education module which contained content pages, self-tests, a quiz and a survey. Details of how the Physicians used the system, their preferences and performance on the assessment were monitored. RESULTS: The learning management system was well received by both Italian and Australian Physicians. Thirty-eight (18 Australian, 20 Italian) Physicians used the system. Participants visited an average of 8.8 pages, with a mean time per hit of 2.9 min. Formative assessment was undertaken by 63.2% and summative assessment by 68.4% of participants. There were no substantial differences in performance between Physicians from both countries. Italian physicians tended to use the system after hours whereas Australian Physicians appear to do so between patient visits. CONCLUSIONS: Simple web-based systems are suitable for delivering educational materials to Primary Care Physicians in a manner likely to be used.

Asthma↗

High IFN-gamma production by CD8+ T cells and early sensitization among infants at high risk of atopy.

BACKGROUND: High genetic risk (HR) of atopy among unstratified populations of infants is associated with attenuated IFN-gamma responses. However, the role of IFN-gamma in progression from HR status to active disease is less clear. OBJECTIVE: To identify immune function markers in neonates with HR that are associated with positive atopic outcomes at 2 years. METHODS: Cord blood mononuclear cells (CBMCs) were collected from 175 children with HR and cryopreserved. The children were assessed for atopy by skin prick at 0.5 and 2 years. CBMCs were thawed and stimulated with allergens and mitogens PHA and staphylococcal enterotoxin B (SEB), and cytokine responses were determined. RESULTS: No correlations were observed between allergen-specific CBMC responses and atopic outcomes. In contrast, sensitization was strongly associated with polyclonal IFN-gamma responses to both PHA (P=.002) and SEB (P=.005), and also with SEB-induced IL-5 (P =.05), IL-10 (P =.02), and IL-13 (P =.01). Logistic regression analysis identified elevated PHA-induced IFN-gamma and SEB-induced IL-13 responses as the strongest independent predictors of atopy development. Cell separation studies confirmed CD8+ T cells as the source of approximately 90% of IFN-gamma production. CONCLUSIONS: IFN-gamma produced by CD8+ T cells may synergize with T(H)2 cytokines in driving atopy development in children with HR.

Allergens↗