Multispecific Aspergillus T cells selected by CD137 or CD154 induce protective immune responses against the most...

Area of Science:

• Mycology
• Immunology
• Hematology

Background:

• Hematopoietic stem cell transplantation (HSCT) patients are susceptible to severe Aspergillus and Mucorales infections.
• Inducing CD4(+) T-helper type 1 (Th1) immunity is a promising strategy against these fungal infections.
• Current immunotherapies are limited by a lack of suitable antigens and broad-spectrum efficacy.

Purpose of the Study:

• To identify Aspergillus fumigatus antigens that elicit protective Th1 immune responses.
• To compare rapid selection protocols for fungus-specific T cells.
• To evaluate the potential for adoptive T-cell transfer in treating invasive fungal infections.

Main Methods:

• Examined immune responses to Aspergillus fumigatus proteins in healthy individuals and HSCT patients.
• Compared CD137 and CD154 expression for rapid selection of fungus-specific T cells.
• Assessed T-cell recognition of naturally processed antigens and cross-reactivity to other fungal species.

Main Results:

• Aspergillus fumigatus proteins Crf1, Gel1, and Pmp20 induced strong Th1 responses in healthy individuals.
• T cells specific for these antigens expanded in HSCT patients with invasive aspergillosis.
• Rapid selection of Th1 cells targeting these antigens was achieved within 24 hours using CD137 or CD154 expression.
• Selected T cells recognized naturally processed antigens and exhibited cross-reactivity to Aspergillus and Mucorales species.

Conclusions:

• Identified key Aspergillus antigens (Crf1, Gel1, Pmp20) for inducing protective Th1 immunity.
• Demonstrated rapid and specific selection of fungus-reactive T cells for potential immunotherapy.
• These findings support the development of adoptive T-cell transfer for prophylaxis or treatment of invasive fungal infections in HSCT patients.