Induction of A. fumigatus-specific CD4-positive T cells in patients recovering from invasive aspergillosis

Abstract

ABSTRACTmade at the Leiden University Medical Center (LUMC, Leiden, The Netherlands). For the production of Catalase1 recombinant protein, three Catalase1 fragments were generated with a 12-amino acid overlap. We used the A. fumigatus strain CBS144.89 for the in-house preparation of Aspergillus crude extract. Commercially available crude extracts of strain CBS192.65 (HAL Allergy, Leiden, The Netherlands) and strain CBS545.65 (Allergon, Ängelholm, Sweden) were also used (see the Online Supplementary Methods for details).

Invasive aspergillosis in acute myeloid leukemia: Are we making progress in reducing mortality?

“…Способность клеток крови человека к про-дукции различных цитокинов в ответ на антигены Aspergillus spp. была продемонстрирована в ряде работ in vitro [40,41,42]. H. Hebart et al изучили динамику синтеза цитокинов у гематологических больных с ИА.…”

“…Установлено, что восстановле-ние Aspergillus-специфических Т-лимфоцитов с фенотипом CD4+CD154+ИФН-γ+ сопрово-ждалось регрессией аспергиллезной инфекции. Эти данные подтверждают, что специфичные для A. fumigatus CD4+Т-клетки необходимы для бла-гоприятного течения ИА у реципиентов ТГСК, и адаптивная иммунотерапия имеет перспективы для использования в лечении ИА [42]. В недавнем исследовании реципиентов ТГСК установлена тенденция к снижению аб-солютного числа Т-хелперов и цитотоксических Т-лимфоцитов в течение 12-месячного перио-да наблюдения [43].…”

Immunoproteomics of Aspergillus for the development of biomarkers and immunotherapies

“…Despite their central role for the regulation of immune responses, the direct analysis of fungus‐specific T cells is challenging, due to their low frequencies (commonly below 0.1% of peripheral blood T cells) and a lack of immunodominant target proteins, due to the complexity of the fungal proteome. Most T‐cell studies are based on indirect assays, using long‐term in vitro antigen provocation and proliferation or effector cytokine production, such as gamma‐interferon (IFN‐γ), as read‐out . These approaches have severe limitations since they do not allow identifying functional subsets within the specific cells and may underestimate the actual frequencies since cytokines are produced only by some of the reactive T cells.…”

Adoptive T‐cell therapy for fungal infections in haematology patients

“…In HSCT patients, A. fumigatus ‐specific T‐cell immunity is defective for up to a year following transplantation, correlating with the period when patients are at highest risk of infection 33 , 43 . In a recent study by Jolink et al, A. fumigatus Crf1 and Catalase‐1‐specific CD4 + T cells were detected in the blood of patients recovering from invasive aspergillosis, but not in patients with progressive disease 44 . Consistent with the observations in transplant patients, an inverse correlation between CD4 + T‐cell numbers and the incidence of IFDs has been observed in HIV‐infected patients 28 .…”