CD4+ and CD8+ type-2 cells are enriched in sputum during COPD eosinophilic exacerbations

Eosinophilic exacerbations account for a quarter of COPD exacerbations but the cellular mechanisms are poorly defined. <bold>Objective:</bold> To determine the relationship between sputum type-2 polarised CD4⁺ & 8⁺ T cells with eosinophils in COPD. <bold>Method:</bold> We performed cytometry on spontaneous sputum from moderate-severe COPD patients; 30 during clinical stability; 21 during exacerbation. We measured viable CD4⁺ & CD8⁺ CRTH2⁺ CD161⁻ (conventional type-2) T cells & subsets co-expressing CD161 (TH2-A or CD161⁺ TC2, respectively) and reported as median [IQR]. Eosinophils were defined as viable, CD16⁻CD193⁺CD294⁺FcεR1a⁻. We divided samples into with (eos) or without (non-eos) elevated sputum eosinophils (≥2% of viable CD45⁺ leukocytes). <bold>Results:</bold> At clinical stability, conventional TH2% was increased in eos vs non-eos sputum (n=18, 0.6 [0.33-1.8] vs n=12, 0.2% [0.09-0.4], p=0.008) & correlated with eosinophil % (n=30, r=0.45, p=0.013). At exacerbation, TH2% (0.9% [0.6-2.4] vs 0.1% [0.03-0.2] p=0.001), TH2-A% (0.8% [0.5-1.4] vs 0.1% [0-0.2], p=0.0015), TC2% (9.3% [4.1-29.6] vs 1.2% [0.7-3.4], p=0.0005) and CD161+ TC2% (1.2% [0.2-3.7] vs 0% [0-0.3], p=0.012) were increased in eos (n=7) vs non-eos (n=14) sputum, respectively. Sputum TH2% (r=0.52, p=0.015), TH2-A% (r=0.54, p=0.01) & TC2% (r=0.59, p=0.005) were positively correlated with eosinophils at exacerbation (n=21). In eos sputum, there was greater T2 skewing in CD8⁺ than in CD4⁺, both at stability (n=18, 3% [1.7-10.7] vs 0.6% [0.3-1.7], p=0.04) and exacerbation (n=7, 9.3% [4-30] vs 0.9% [0.6-2.4], p=0.04), respectively. <bold>Conclusion:</bold> CD4⁺ & CD8⁺ type-2 T cells likely contribute to eosinophilic exacerbations & warrant greater spatial & functional understanding.