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

Yolanda Gonzalez,María Teresa Herrera,Esmeralda Juárez,Miguel Angel Salazar-Lezama,Martha Torres,Karen Bobadilla,Rasheed Ahmad

doi:10.1371/journal.pone.0123591

Abstract

Alveolar resident memory T cells (TRM) 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.

Highlights

In recent years, evidence has accumulated supporting a role for innate and adaptive immune cells in maintaining lung health, and it has been reported that T cell populations play an important role in pathogen immune surveillance [1]
A subset of CD3+CD161+ T lymphocytes resides in the bronchoalveolar space
Previous studies have identified a subpopulation of T lymphocytes, CD3+CD161+, with the capacity to migrate from peripheral blood to tissue under steady-state conditions

Summary

Introduction

Evidence has accumulated supporting a role for innate and adaptive immune cells in maintaining lung health, and it has been reported that T cell populations play an important role in pathogen immune surveillance [1]. Lung airway CD3+ T cells express the memory CD45RO+ antigen, but TRM comprise a mixture of subpopulations that have not been fully characterized. CD3+CD161+ T Cells Are Resident Memory T Cells (TRM) in the Lung maintained by the continual recruitment of new cells from the lymph nodes and blood [2]. Despite the functional capabilities of CD161+ T cells, these cells have been consistently reported to express the memory antigen CD45RO [6, 7]. Whereas the majority of CD4+CD161+ and CD8+CD161+ T cell subsets exhibit a memory cell phenotype (CD45RO+), CD161- T cells comprise mixed populations, which primarily include naïve CD8+ subsets [5] and naïve (26%) and memory (63%) CD4+ subsets

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Results

Conclusion