The bone marrow represents an enrichment site of specific T lymphocytes against filamentous fungi.

Daniela Vallerini,Luigina Romani,Paola Bresciani,Ambra Paolini,Franco Narni,Giovanni Riva,Ivana Lagreca,Monica Morselli,Leonardo Potenza,Roberto Marasca,Tommaso Trenti,Valeria Coluccio,Patrizia Comoli,Elisabetta Colaci,Daniele Campioli,Fabio Forghieri,Chiara Quadrelli,Monica Maccaferri,Mario Luppi,Patrizia Barozzi,Jean Paul Latgé ,Aurora Cuoghi

doi:10.1093/mmy/myv107

Abstract

Bone marrow has already been described as an enrichment site for several antigen-specific T lymphocytes, but the presence of mould-specific T cells has never been investigated in the bone marrow. We have previously demonstrated that mould-specific T cells emerge in the peripheral blood of patients with invasive fungal infections (IFI) but tend to become undetectable after disease resolution. In seven patients with a history of IFI, we investigated the presence of mould-specific T cells secreting different cytokines in bone marrow and peripheral blood paired samples. The results showed that the frequencies of mould-specific T cells secreting the protective cytokine IFNγ are significantly higher in bone marrow (BM) and are mainly represented by CD8+ T lymphocytes with effector phenotype. A putative disappearance of such protective BM responses after myeloablative therapy could contribute to the increased risk of IFI in hematologic patients.

Highlights

Invasive mould infections (IMI), mainly invasive aspergillosis (IA) and invasive mucormycosis (IM), remain a major cause of morbidity and mortality in patients with hematologic malignancies, in particular for acute leukemia patients and hematopoietic stem cell transplant (HSCT) recipients.[1]
At a median time of 12 months after IMI diagnosis, mean frequencies of these conidia-reactive T lymphocytes were generally higher in bone marrow (BM) than in peripheral blood (PB)
We demonstrated that 7 out of 7 patients (100%) showed significantly higher proportions of mould-specific T cells in the BM, compared with the PB. These specific BM immune responses were characterized by high frequencies of protective IFNγ -producing T cells, which still remained detectable several months after IFI complete regression

Summary

Introduction

Invasive mould infections (IMI), mainly invasive aspergillosis (IA) and invasive mucormycosis (IM), remain a major cause of morbidity and mortality in patients with hematologic malignancies, in particular for acute leukemia patients and hematopoietic stem cell transplant (HSCT) recipients.[1] We previously demonstrated that, during the course of either IA or IM, mould-specific T cells may emerge in the peripheral blood (PB) of hematologic patients.[2,3,4] The detection of specific T cells against filamentous fungi in patients’ PB represents an alternative diagnostic marker of IMI5 and seems to correlate with disease course These mould-specific T cells tend to become undetectable in the PB after disease resolution.[3,4].

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Results

Conclusion