CD161 Expression Defines a Th1/Th17 Polyfunctional Subset of Resident Memory T Lymphocytes in Bronchoalveolar Cells

Alveolar resident memory T cells (T(RM)) comprise a currently uncharacterized mixture of cell subpopulations. The CD3(+)CD161(+) T cell subpopulation resides in the liver, intestine and skin, but it has the capacity for tissue migration; however, the presence of resident CD3(+)CD161(+) T cells in the bronchoalveolar space under normal conditions has not been reported. Bronchoalveolar cells (BACs) from healthy volunteers were evaluated and found that 8.6% (range 2.5%-21%) of these cells were CD3(+) T lymphocytes. Within the CD3(+) population, 4.6% of the cells (2.1-11.3) expressed CD161 on the cell surface, and 74.2% of the CD161(+)CD3(+) T cells expressed CD45RO. The number of CD3(+)CD161(+) T cells was significantly lower in the bronchoalveolar space than in the blood (4.6% of BACs vs 8.4% of peripheral blood mononuclear cells (PBMCs); P<0.05). We also found that 2.17% of CD4(+) T lymphocytes and 1.52% of CD8(+) T lymphocytes expressed CD161. Twenty-two percent of the alveolar CD3(+)CD161(+) T lymphocytes produced cytokines upon stimulation by PMA plus ionomycin, and significantly more interferon gamma (IFN-γ) was produced compared with other cytokines (P = 0.05). Most alveolar CD3(+)CD161(+) T cells produced interleukin-17 (IL-17) and IFN-γ simultaneously, and the percentage of these cells was significantly higher than the percentage of CD3(+)CD161- T cells. Moreover, the percentage of alveolar CD3(+)CD161(+) T lymphocytes that produced IFN-γ/IL-17 was significantly higher than those in the peripheral blood (p<0.05). In conclusion, Th1/Th17-CD3(+)CD161(+) TRM could contribute to compartment-specific immune responses in the lung.