Clinical-scale isolation of the total Aspergillus fumigatus–reactive T–helper cell repertoire for adoptive transfer

Bächer, Petra; Jochheim-Richter, Andrea; Mockel-Tenbrink, Nadine; Kniemeyer, Olaf; Wingenfeld, Eva; Alex, Regina; Ortigao, A.; Karpova, Darja; Lehrnbecher, Thomas; Ullmann, Andrew J.; Hamprecht, Axel; Cornely, Oliver A.; Brakhage, Axel A.; Assenmacher, Mario; Bönig, Halvard; Scheffold, Alexander

doi:10.1016/j.jcyt.2015.05.011

Cited by 32 publications

(26 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The adaptive antifungal immune response in humans, particularly CD4 + T cells recognizing Aspergillus antigens, have gained increasing attention for both, as noninvasive diagnostic targets to monitor invasive fungal growth and identifying patients at risk, and for potentially contributing to the protection against fungal infections [32, 33]. Evidence for the latter, however, is sparse [5,34].…”

Section: Discussionmentioning

confidence: 99%

The domestic pig as human‐relevant large animal model to study adaptive antifungal immune responses against airborne Aspergillus fumigatus

et al. 2020

Self Cite

View full text Add to dashboard Cite

Pulmonary mucosal immune response is critical for preventing opportunistic Aspergillus fumigatus infections. Although fungus‐specific CD4+ T cells in blood are described to reflect the actual host–pathogen interaction status, little is known about Aspergillus‐specific pulmonary T‐cell responses. Here, we exploit the domestic pig as human‐relevant large animal model and introduce antigen‐specific T‐cell enrichment in pigs to address Aspergillus‐specific T cells in the lung compared to peripheral blood. In healthy, environmentally Aspergillus‐exposed pigs, the fungus‐specific T cells are detectable in blood in similar frequencies as observed in healthy humans and exhibit a Th1 phenotype. Exposing pigs to 106 cfu/m3 conidia induces a long‐lasting accumulation of Aspergillus‐specific Th1 cells locally in the lung and also systemically. Temporary immunosuppression during Aspergillus‐exposure showed a drastic reduction in the lung‐infiltrating antifungal T‐cell responses more than 2 weeks after abrogation of the suppressive treatment. This was reflected in blood, but to a much lesser extent. In conclusion, by using the human‐relevant large animal model the pig, this study highlights that the blood clearly reflects the mucosal fungal‐specific T‐cell reactivity in environmentally exposed as well as experimentally exposed healthy pigs. But, immunosuppression significantly impacts the mucosal site in contrast to the initial systemic immune response.

show abstract

Section: Discussionmentioning

confidence: 99%

The domestic pig as human‐relevant large animal model to study adaptive antifungal immune responses against airborne Aspergillus fumigatus

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…indicated by the correlation of the presence of Aspergillus-specific T cells with a T-helper (Th) 1 phenotype with the clearance of the Aspergillus infection in patients after allogeneic stem cell transplantation [23]. As a result, transfer of specific T cells has been suggested as a therapeutic or prophylactic treatment option [24][25][26][27][28][29][30][31][32]. T cells are also important in the even higher number of immunocompetent patients, in particular, those with impaired lung function that are affected by noninvasive Aspergillus-related clinical complications.…”

Section: The Adaptive Immune System and Aspergillus Infectionsmentioning

confidence: 99%

Immunoproteomics of Aspergillus for the development of biomarkers and immunotherapies

Kniemeyer

Ebel²,

Krüger

et al. 2016

Proteomics Clinical Apps

Self Cite

View full text Add to dashboard Cite

Filamentous fungi of the genus Aspergillus play significant roles as pathogens causing superficial and invasive infections as well as allergic reactions in humans. Particularly invasive mycoses caused by Aspergillus species are characterized by high mortality rates due to difficult diagnosis and insufficient antifungal therapy. The application of immunoproteomic approaches has a great potential to identify new targets for the diagnosis, therapy, and vaccine development of diseases caused by Aspergillus species. Serological proteome analyses (SERPA) that combine 2D electrophoresis with Western blotting are still one of the most popular techniques for the identification of antigenic proteins. However, recently a growing number of approaches have been developed to identify proteins, which either provoke an antibody response or which represent targets of T-cell immunity in patients with allergy or fungal infections. Here, we review advances in the studies of immune responses against pathogenic Aspergilli as well as the current status of diagnosis and immunotherapy of Aspergillus infections.

show abstract

“…fumigatus , specific effector/memory CD4 T cells derived from peripheral blood of healthy adult donors displayed a Th1 phenotype 16 and A . fumigatus -expanded Th1 cells are currently being tested for adoptive therapy upon stem cell transplantation 17 (Trail EudraCT 2013-002914-11). However, lung-derived Aspergillus -specific T cells of the effector/memory subpopulation show a Th17 phenotype with notably production of IL-17 18 , implicating the involvement of a complex adaptive immune response in clearance of fungal pathogens.…”

Section: Introductionmentioning

confidence: 99%

Developmental induction of human T-cell responses against Candida albicans and Aspergillus fumigatus

Vogel

Pierau

Arra

et al. 2018

Sci Rep

View full text Add to dashboard Cite

The origin of human T-cell responses against fungal pathogens early in life is not clearly understood. Here, we show that antifungal T-cell responses are vigorously initiated within the first years of life against lysates and peptides of Candida albicans or Aspergillus fumigatus, presented by autologous monocytes. The neonatal responding T-cell pool consists of 20 different TCR-Vβ families, whereas infant and adult pools display dramatically less variability. Although we demonstrate no bias for anti-fungal IL-4 expression early in life, there was a strong bias for anti-fungal IL-17 production. Of note, only T-cells from neonates and infants show an immediate co-expression of multiple cytokines. In addition, only their T-cells co-express simultaneously transcription factors T-bet and RORγt in response to fungi and subsequently their target genes IL-17 and IFNγ. Thus, T-cells of neonates and infants are predetermined to respond quickly with high plasticity to fungal pathogens, which might give an excellent opportunity for therapeutic interventions.

show abstract

Clinical-scale isolation of the total Aspergillus fumigatus–reactive T–helper cell repertoire for adoptive transfer

Cited by 32 publications

References 35 publications

The domestic pig as human‐relevant large animal model to study adaptive antifungal immune responses against airborne Aspergillus fumigatus

The domestic pig as human‐relevant large animal model to study adaptive antifungal immune responses against airborne Aspergillus fumigatus

Immunoproteomics of Aspergillus for the development of biomarkers and immunotherapies

Developmental induction of human T-cell responses against Candida albicans and Aspergillus fumigatus

Contact Info

Product

Resources

About