Multispecific Aspergillus T Cells Selected by CD137 or CD154 Induce Protective Immune Responses Against the Most Relevant Mold Infections

Stuehler, Claudia; Nowakowska, Justyna; Bernardini, Claudia; Topp, Max S.; Battegay, Manuel; Passweg, Jakob; Khanna, Nina

doi:10.1093/infdis/jiu607

Cited by 46 publications

(44 citation statements)

References 42 publications

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“…This also precludes the use of multimerized peptide-MHC complexes for isolation of A. fumigatusespecific T cells. Although we and others observed that some isolated A. fumigatus proteins predominantly induce T H 1 responses in healthy individuals, further investigations are needed until these findings could be applied clinically [15,20,21,26]. To overcome the lack of defined antigens for T-cell stimulation, we established a protocol by using a GMP-grade soluble lysate from A. fumigatus, containing the whole spectrum of potential T-cell epitopes.…”

Section: Discussionmentioning

confidence: 99%

“…This abrogates the risk for phenotypical and functional changes as might occur during a longterm stimulation process (>24 h) [14]. Among several markers described, CD154 (CD40L) and CD137 (4-1BB) fulfill these criteria for CD4þ T cells [14,19,20]. Qualitative differences of expanded A. fumigatusereactive cells selected by CD154 or CD137 were extensively compared in preclinical runs.…”

Section: Depletion Of Cd8þ and Tregsmentioning

confidence: 99%

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

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Section: Depletion Of Cd8þ and Tregsmentioning

confidence: 99%

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

et al. 2015

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“…CD40L is a specific marker of CD4+ T cells that have been engaged via T cell receptor stimulation [27]. Impaired expression of CD40L in CD4+ T cells has been reported in HIV-infected individuals compared to healthy controls in response to super-antigen staphylococcal enterotoxin B in vitro [28].…”

Section: Discussionmentioning

confidence: 99%

The induction of CD80 and apoptosis on B cells and CD40L in CD4+ T cells in response to seasonal influenza vaccination distinguishes responders versus non-responders in healthy controls and aviremic ART-treated HIV-infected individuals

Powell

Luo

Martin

et al. 2017

Vaccine

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Background Studies have shown that HIV infection is associated with an impaired influenza vaccine response. We examined the role of cellular phenotypes and function in influenza vaccine responsiveness in healthy controls and aviremic HIV-infected subjects on antiretroviral treatment (ART). Methods 16 healthy controls and 26 ART+ aviremic HIV+ subjects were enrolled in the current study. Blood was collected at pre-vaccination (D0), and on days 7–10 (D7) and 14–21 (D14) following the 2013–2014 seasonal influenza vaccine administrations. Subjects were classified as responders if neutralizing titers against H1N1 virus increased ≥ 4-fold at D14 compared to D0. A serial analysis of B and CD4+ T cell frequencies and activation was performed on D0 and D7 by flow cytometry. Results 9 of 26 (34.6%) HIV-infected individuals and 7 of 16 (43.8%) healthy controls were classified as responders to influenza vaccines. Total B cell apoptosis (annexin V) was increased on D7 post-vaccination in non-responders but not in responders among both controls and HIV+ subjects. Surface CD80 expression on memory B cells and intracellular CD40L expression on memory CD4+ T cells were induced on D7 in responders of controls but not in non-responders. The CD80 and CD40L induction was not demonstrable in HIV-infected subjects regardless of responders and non-responders. Memory CD4+ T cell cycling tended to increase on D7 in the four study groups but did not achieve significance. All the other parameters were indistinguishable between responders and non-responders, regardless of HIV-infection status. Conclusion The perturbation of activation and apoptotic induction on B cells or CD4+ T cells after seasonal influenza vaccination in non-responders and HIV-infected subjects may help understand the mechanism of impaired vaccine responsiveness.

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“…This technique has been used to generate Aspergillus -specific T cells, with in vitro activity against a wide range of fungal isolates [67]. In a further refinement, adoptive transfer of chimeric antigen receptor (CAR) T cells targeting tumor antigens has been adapted to target fungal pathogens [68].…”

Section: Leukocyte Transfusionsmentioning

confidence: 99%

Modulating host immune responses to fight invasive fungal infections

Scriven

Tenforde

Levitz

et al. 2017

Current Opinion in Microbiology

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Modulation of host immunity in invasive fungal infection is an appealing but as yet mostly elusive treatment strategy. Animal studies in invasive candidiasis and aspergillosis have demonstrated beneficial effects of colony stimulating factors, interferon-gamma and monoclonal antibodies. More recent studies transfusing leukocytes pre-loaded with lipophilic anti-fungal drugs, or modulated T-cells, along with novel vaccination strategies show great promise. The translation of immune therapies into clinical studies has been limited to date but this is changing and the results of new Candida vaccine trials are eagerly awaited. Immune modulation in HIV-associated mycoses remains complicated by the risk of immune reconstitution inflammatory syndrome and although exogenous interferon-gamma therapy may be beneficial in cryptococcal meningitis, early initiation of anti-retroviral therapy leads to increased mortality. Further study is required to better target protective immune responses.

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Multispecific Aspergillus T Cells Selected by CD137 or CD154 Induce Protective Immune Responses Against the Most Relevant Mold Infections

Abstract: These findings may form the basis for adoptive T-cell transfer for prophylaxis or treatment in patients with these devastating infections.

Cited by 46 publications

References 42 publications

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

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

The induction of CD80 and apoptosis on B cells and CD40L in CD4+ T cells in response to seasonal influenza vaccination distinguishes responders versus non-responders in healthy controls and aviremic ART-treated HIV-infected individuals

Modulating host immune responses to fight invasive fungal infections

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