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CD8(+) T cells implicated in the pathogenesis of allergic fungal rhinosinusitis
1Department of Surgery, Otolaryngology Head and Neck Surgery, University of Adelaide, Adelaide, South Australia, Australia.
Abstract:
Fungi in paranasal sinuses are characteristic and considered a major pathogenic factor in a subset of chronic rhinosinusitis (CRS) patients, known as allergic fungal rhinosinusitis (AFRS). CD8(+) T cells are enriched in AFRS sinuses but their role in fungal-specific responses is unknown. Alternaria alternata- and Aspergillus fumigatus-specific T lymphocyte responses were investigated in 6 AFRS patients, 10 eosinophilic mucus CRS (EMCRS) patients, 10 CRS with nasal polyps (CRSwNPs) patients, 6 allergic rhinitis with fungal allergy (ARFA) patients, and five controls. Fungal-specific proliferation of human peripheral blood mononuclear cells (PBMCs) was studied prospectively. Proliferating cells were examined for CD3, CD4, CD8, and CD25 expression. Relevant clinical characteristics, fungal allergy, detection of fungi in sinuses, and CD4(+) and CD8(+) composition of sinus T cells were also examined. CD4(+) T-cell division to fungi occurred in all samples, regardless of fungal allergy or CRS. Fungal-specific CD8(+) T-cell division occurred in all ARFA and control samples and the majority of CRSwNP patients; however, CD8(+) T cells failed to proliferate in AFRS and EMCRS patients. The CD8(+) T cells from AFRS patients also did not up-regulate the activation marker, CD25, with fungal antigen exposure. Presence of A. alternata- and A. fumigatus-specific CD4(+) and CD8(+) T-cell proliferation in healthy individuals, ARFA, and CRSwNP patients suggests that both T-cell subsets may be important in immune responses to these fungi. In AFRS and EMCRS patients, only fungal-specific CD4(+) T-cell proliferation occurred; hence, a lack of CD8(+) T-cell proliferation and activation in the presence of sinus eosinophilic mucus in these patients, regardless of fungal allergy, is a novel finding. This raises the question whether a dysfunctional CD8(+) T-cell response predisposes to ineffective clearance and accumulation of fungi in the sinuses of susceptible patients.
Insights
In allergic fungal rhinosinusitis (AFRS) and eosinophilic mucus CRS (EMCRS), CD8(+) T cells fail to respond to fungi. This dysfunction may lead to ineffective fungal clearance in the sinuses.
Area of Science:
- Immunology
- Rhinology
- Microbiology
Background:
- Fungi are pathogenic in chronic rhinosinusitis (CRS), particularly allergic fungal rhinosinusitis (AFRS).
- CD8(+) T cells are abundant in AFRS sinuses, but their role in fungal immunity is unclear.
Purpose of the Study:
- To investigate fungal-specific T lymphocyte responses, focusing on CD8(+) T cells, in various CRS subtypes and controls.
- To determine if CD8(+) T cell dysfunction is associated with AFRS and eosinophilic mucus CRS (EMCRS).
Main Methods:
- Fungal-specific proliferation of peripheral blood mononuclear cells (PBMCs) from AFRS, EMCRS, CRS with nasal polyps (CRSwNPs), allergic rhinitis with fungal allergy (ARFA), and control groups was analyzed.
- Expression of CD3, CD4, CD8, and CD25 on proliferating T cells was assessed.
- Clinical data, fungal allergy status, and sinus fungal presence were correlated with T cell responses.
Main Results:
- CD4(+) T cell proliferation to fungi occurred in all patient groups and controls.
- Fungal-specific CD8(+) T cell proliferation was observed in ARFA, controls, and most CRSwNP patients.
- Notably, CD8(+) T cells from AFRS and EMCRS patients failed to proliferate or upregulate CD25 (activation marker) upon fungal antigen exposure.
Conclusions:
- Functional CD8(+) T cell responses to common fungi (Alternaria alternata, Aspergillus fumigatus) are present in healthy individuals and some CRS patients.
- A lack of CD8(+) T cell proliferation and activation in AFRS and EMCRS patients suggests a potential defect in cellular immunity.
- This CD8(+) T cell dysfunction may contribute to ineffective fungal clearance and disease pathogenesis in susceptible individuals.
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