Spontaneous Development of Dacryoadenitis in Mice Deficient for Programmed Cell Death-1

Abstract

Purpose: : Programmed cell death-1 (PD-1, pdcd1) is one of the costimulatory molecules expressed on T lymphocyte and delivers a negative signal to T lymphocytes. It has been reported recently that PD-1-deficient C57BL/6 mice spontaneously develop lupus-like glomerulonephritis and arthritis via hyperactivation of lymphocytes. In this study, we investigated whether pdcd1^-/- mice also induce dacryoadenitis, and if so, what types of inflammatory cells infiltrate into the lacrimal gland.

Methods: : Lacrimal glands were obtained from 6-month-old pdcd1^+/+, pdcd1^+/-, or pdcd1^-/- mice and hematoxylin-eosin stained sections were prepared for histopathological analysis. In addition, lacrimal glands of each group were homogenized, and single cell suspensions were purified for flow cytometric analysis using monoclonal antibodies to CD4, CD8, CD11b, CD11c, and CD45R.

Results: : Although development of dacryoadenitis was not observed in any of the pdcd1^+/+ or pdcd1^+/- mice, all pdcd1^-/- mice spontaneously developed severe inflammation in the lacrimal gland. Inflammatory cells infiltrating into lacrimal glands of pdcd1^-/- mice consisted of mainly neutrophils, CD4⁺T cells, CD8⁺T cells and B cells, and with some macrophages and dendritic cells.

Conclusions: : These results indicate that PD-1 plays a pivotal role for regulating spontaneous development of dacryoadenitis. Dacryoadenitis occurred in pdcd1^-/- mice

Keywords: immunomodulation/immunoregulation • inflammation • inhibitory receptors