Platelets regulate CD4+ T-cell differentiation via multiple chemokines in humans

Norbert Gerdes; Linjing Zhu; Maria Ersoy; Andreas Hermansson; Paul Hjemdahl; Hu Hu; Göran K. Hansson; Nailin Li

doi:10.1160/TH11-01-0020

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2011; 106(02): 353-362
DOI: 10.1160/TH11-01-0020

Platelets and Blood Cells

Schattauer GmbH

Platelets regulate CD4⁺ T-cell differentiation via multiple chemokines in humans

Norbert Gerdes^*

¹Experimental Cardiovascular Research Unit at the Center for Molecular Medicine - Solna, Karolinska Institute, Stockholm, Sweden

⁴Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany

,

Linjing Zhu^*

²Clinical Pharmacology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden

³Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China

,

Maria Ersoy

²Clinical Pharmacology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden

,

Andreas Hermansson

¹Experimental Cardiovascular Research Unit at the Center for Molecular Medicine - Solna, Karolinska Institute, Stockholm, Sweden

,

Paul Hjemdahl

²Clinical Pharmacology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden

,

Hu Hu

³Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China

,

Göran K. Hansson

¹Experimental Cardiovascular Research Unit at the Center for Molecular Medicine - Solna, Karolinska Institute, Stockholm, Sweden

,

Nailin Li

²Clinical Pharmacology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden

› Author Affiliations

Abstract

Summary

Atherosclerosis is an inflammatory and thrombotic disease. Both platelets and lymphocytes play important roles in atherogenesis. However, information on their interaction is limited. We therefore studied how platelets regulate CD4⁺ T cell activation and differentiation. Human CD4⁺ T cells and autologous platelets were co-cultured. Platelets concentration-dependently enhanced anti-CD3/CD28-induced IFNγ production by CD4⁺ T cells, but attenuated their proliferation. Abrogation of heterotypic cell-cell contact partially reversed the enhancement, and supernatant from activated platelets partially mimicked the enhancement, suggesting that platelets exert their effects via both soluble mediators and direct cell-cell contact. Platelets enhanced the production of IL-10 and cytokines characteristic for type 1 T helper (T_H1) (IFN_γ/ TNFα) and T_H17 (IL-17) cells, but influenced T_H2 cytokines (IL-4/IL-5) little. The cytokine responses were accompanied by enhanced T_H1/T_H17/T_Reg differentiation. Using neutralising antibodies and recombinant PF4, RANTES, and TGFβ, we found that platelet-derived PF4 and RANTES enhanced both pro- and anti-inflammatory cytokine production, whilst recombinant TGFβ enhanced IL-10 but not TNFα production. In conclusion, platelets enhance the differentiation and cytokine production of anti-CD3/CD28-stimulated CD4⁺ T cells via both multiple chemokines and direct cell-cell contact. Our study provides new insights into the cross-talk between thrombosis and adaptive immunity, and indicates that platelets can enhance T-effector cell development.

Keywords

Platelets - CD4⁺ T cells - regulatory T cells - T_H17 cells - adaptive immunity

Full Text

References

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