This study highlights the following findings: (i) CD8+ T cells, in addition to CD4+ T cells, represent a cellular source for 1,25(OH)2D3-induced AAT in the airway microenvironment, (ii) TGF-β acts as a co-factor in this vitamin D controlled regulatory axis and (iii) this axis is defective in PiZZ patients with severe AAT deficiency. Here, CD8A is linked to alpha 1-antitrypsin deficiency.