Background: A subset of COPD patients (-pts) has eosinophilia, a trait targeted in clinical drug programs. Yet, little is known about the immunological millieu associated with infiltration of eosinophils (EOS) into COPD lungs.
Aim: To compare the T cell profile between COPD-pts with high (EOShi) and low (EOSlow) tissue eosinophilia.
Methods: EOS were detected in tissue sections from surgically removed lungs from 39 COPD-pts (GOLD I-IV) and 15 non-COPD controls using immunohistochemistry. A subset of the samples underwent single cell transcription factor-based CD4 and CD8 T cell profiling using multiplex immunofluorescence and computerized image analysis. We compared different anatomic lung regions: alveolar tissue (ALV), small airways (SAW) and pulmonary blood vessels (BV).
Results: Median total tissue EOS (%) was significantly increased in COPD-pts (0.41 vs. 0.07, p<0.0001), and the EOS infiltration pattern was generally patchy. Both CD4 and CD8 T cells had complex, partly overlapping and microenvironmentally dictated transcription factor profiles. The EOShi group tended to have the highest CD4/CD8 ratio in the whole tissue section and BV regions, while the EOSlow group tended to have the highest ratio in the ALV and SAW regions. Both CD4 and CD8 cells commonly expressed the type-2 promoting transcription factor GATA-3. CD4+/GATA-3+ and CD8+/GATA-3+ cells tended to be increased in the EOShi when compared to the EOSlow group in the whole tissue and in all regions except for ALV.
Conclusion: EOS infiltration is common in COPD lungs and seemingly linked to complex T cell transcription factor profiles, where variants of GATA-3+ CD4 and CD8 populations may have important regulatory roles.