Species Difference of CD137 Ligand Signaling in Human and Murine Monocytes

Qianqiao Tang,Zhe Shao,Dongsheng Jiang,Julia M Martínez Gómez,Herbert Schwarz,Rafael Linden

doi:10.1371/journal.pone.0016129

Abstract

BackgroundStimulation of CD137 ligand on human monocytes has been shown to induce DC differentiation, and these CD137L-DCs are more potent than classical DCs, in stimulating T cell responses in vitro. To allow an in vivo evaluation of the potency of CD137L-DCs in murine models we aimed at generating murine CD137L-DCs.Methodology/Principal FindingsWhen stimulated through CD137 ligand murine monocytes responded just as human monocytes with an increased adherence, morphological changes, proliferation and an increase in viable cell numbers. But CD137 ligand signaling did not induce expression of inflammatory cytokines and costimulatory molecules in murine monocytes and these cells had no T cell stimulatory activity. Murine monocytes did not differentiate to inflammatory DCs upon CD137 ligand signaling. Furthermore, while CD137 ligand signaling induces maturation of human immature classical DCs it failed to do so with murine immature classical DCs.Conclusions/SignificanceThese data demonstrate that both human and murine monocytes become activated by CD137 ligand signaling but only human and not murine monocytes differentiate to inflammatory DCs.

Highlights

Mice have long been invaluable in helping immunologists to understand how immunity works, especially when systemic effects of immune modulations were studied
Recombinant CD137 protein as a sole factor is sufficient to induce human monocyte to DC differentiation and these CD137L-DCs are more potent than classical DCs in inducing proliferation, IFNc secretion and perforin expression by T cells [20]
In response to CD137 ligand signaling the cells attached to the plates, spread and formed lamellipodia (Figure 1A), similar to what has been shown for human monocytes [7]

Summary

Introduction

Mice have long been invaluable in helping immunologists to understand how immunity works, especially when systemic effects of immune modulations were studied Many immunotherapeutic approaches, such as neutralization of inflammatory cytokines for treatment of autoimmune disease have been pioneered in mice [1]. Differences exist between the human and murine immune system. CD14 and CD16 are not suitable to distinguish murine monocyte subpopulations. In the murine system monocyte subpopulations are classified as CD115+, Ly6Chigh and CD115+, Ly6Clow, respectively, which constitute 50% each [3]. Stimulation of CD137 ligand on human monocytes has been shown to induce DC differentiation, and these CD137L-DCs are more potent than classical DCs, in stimulating T cell responses in vitro. To allow an in vivo evaluation of the potency of CD137L-DCs in murine models we aimed at generating murine CD137L-DCs

Methods

Results

Conclusion