CD8A and chronic obstructive pulmonary disease: Based on our collective cytokine data, we propose that two largely independent types of lung CD4+ T cell dysfunction develop in some susceptible smokers and contribute to development of individually variable in COPD phenotypes: (1) deficient CD4+ T cell elaboration of IL-10, which fails to check auto-aggressive activities of lung CD8 and NK cells leading to emphysema; and (2) pervasive loss of CD4+ T cell polarization, which leads to non-emphysematous pathologies that cause airflow obstruction.