Details

Autor(en) / Beteiligte

• Habiel, David M.
• Espindola, Milena S.
• Kitson, Chris
• Azzara, Anthony V.
• Coelho, Ana Lucia
• Stripp, Barry
• Hogaboam, Cory M.

Titel

Characterization of CD28null T cells in idiopathic pulmonary fibrosis

Ist Teil von

• Mucosal immunology, 2019, Vol.12 (1), p.212-222

Ort / Verlag

New York: Nature Publishing Group US

Erscheinungsjahr

2019

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease, with unknown etiopathogenesis and suboptimal therapeutic options. Previous reports have shown that increased T-cell numbers and CD28 null phenotype is predictive of prognosis in IPF, suggesting that these cells might have a role in this disease. Flow cytometric analysis of explanted lung cellular suspensions showed a significant increase in CD8 + CD28 null T cells in IPF relative to normal lung explants. Transcriptomic analysis of CD3 + T cells isolated from IPF lung explants revealed a loss of CD28-transcript expression and elevation of pro-inflammatory cytokine expression in IPF relative to normal T cells. IPF lung explant-derived T cells (enriched with CD28 null T cells), but not normal donor lung CD28 + T cells induced dexamethasone-resistant lung remodeling in humanized NSG mice. Finally, CD28 null T cells expressed similar CTLA4 and significantly higher levels of PD-1 proteins relative to CD28 + T cells and blockade of either proteins in humanized NSG mice, using anti-CTLA4, or anti-PD1, mAb treatment-accelerated lung fibrosis. Together, these results demonstrate that IPF CD28 null T cells may promote lung fibrosis but the immune checkpoint proteins, CTLA-4 and PD-1, appears to limit this effect.