CD4+ T Cells in the Lungs of Acute Sarcoidosis Patients Recognize an Aspergillus Nidulans Epitope

Authors

Sarah A. Greaves, University of Colorado Anschutz Medical Campus
Avinash Ravindran, Karolinska University Hospital, Karolinska Institutet
Radleigh Santos, Nova Southeastern UniversityFollow
Lan Chen, University of Colorado Anschutz Medical Campus
Michael T. Falta, University of Colorado Anschutz Medical Campus
Yang Wang, University of Colorado Anschutz Medical Campus
Angela M. Mitchell, University of Colorado Anschutz Medical Campus
Shaikh M. Atif, University of Colorado Anschutz Medical Campus
Douglas G. Mack, University of Colorado Anschutz Medical Campus
Alex N. Tinega, University of Colorado Anschutz Medical Campus
Lisa A. Maier, University of Colorado Anschutz Medical Campus, National Jewish Health
Shaodong Dai, University of Colorado Anschutz Medical Campus
Clemencia Pinilla, Florida International University
Johan Grunewald, Karolinska University Hospital
Andrew P. Fontenot, University of Colorado Anschutz Medical Campus

Document Type

Article

Publication Date

8-19-2021

Publication Title

Journal of Experimental Medicine

Keywords

Mucosal immunology

ISSN

1540-9538

Volume

218

Issue/No.

10

First Page

e20210785

Abstract

Löfgren’s syndrome (LS) is an acute form of sarcoidosis characterized by a genetic association with HLA-DRB1*03 (HLA-DR3) and an accumulation of CD4⁺ T cells of unknown specificity in the bronchoalveolar lavage (BAL). Here, we screened related LS-specific TCRs for antigen specificity and identified a peptide derived from NAD-dependent histone deacetylase hst4 (NDPD) of Aspergillus nidulans that stimulated these CD4⁺ T cells in an HLA-DR3–restricted manner. Using ELISPOT analysis, a greater number of IFN-γ– and IL-2–secreting T cells in the BAL of DR3⁺ LS subjects compared with DR3⁺ control subjects was observed in response to the NDPD peptide. Finally, increased IgG antibody responses to A. nidulans NDPD were detected in the serum of DR3⁺ LS subjects. Thus, our findings identify a ligand for CD4⁺ T cells derived from the lungs of LS patients and suggest a role of A. nidulans in the etiology of LS.

Comments

© 2021 Greaves et al.

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.

NSUWorks Citation

Greaves, Sarah A.; Ravindran, Avinash; Santos, Radleigh; Chen, Lan; Falta, Michael T.; Wang, Yang; Mitchell, Angela M.; Atif, Shaikh M.; Mack, Douglas G.; Tinega, Alex N.; Maier, Lisa A.; Dai, Shaodong; Pinilla, Clemencia; Grunewald, Johan; and Fontenot, Andrew P., "CD4+ T Cells in the Lungs of Acute Sarcoidosis Patients Recognize an Aspergillus Nidulans Epitope" (2021). Mathematics Faculty Articles. 315.
https://nsuworks.nova.edu/math_facarticles/315

ORCID ID

0000-0002-8194-5502

DOI

10.1084/jem.20210785