CD80 on Human T Cells Is Associated With FoxP3 Expression and Supports Treg Homeostasis.

Blagoje Soskic,Louisa E Jeffery,Alan Kennedy,David H Gardner,Neil Halliday,Gideon M Hirschfield,Daniel Janman,David M Sansom,Behzad Rowshanravan,Cayman Williams,Tie Zheng Hou

doi:10.3389/fimmu.2020.577655

Abstract

CD80 and CD86 are expressed on antigen presenting cells (APCs) and their role in providing costimulation to T cells is well established. However, it has been shown that these molecules can also be expressed by T cells, but the significance of this observation remains unknown. We have investigated stimuli that control CD80 and CD86 expression on T cells and show that in APC-free conditions around 40% of activated, proliferating CD4+ T cells express either CD80, CD86 or both. Expression of CD80 and CD86 was strongly dependent upon provision of CD28 costimulation as ligands were not expressed following TCR stimulation alone. Furthermore, we observed that CD80+ T cells possessed the hallmarks of induced regulatory T cells (iTreg), expressing Foxp3 and high levels of CTLA-4 whilst proliferating less extensively. In contrast, CD86 was preferentially expressed on INF-γ producing cells, which proliferated more extensively and had characteristics of effector T cells. Finally, we demonstrated that CD80 expressed on T cells inhibits CTLA-4 function and facilitates the growth of iTreg. Together these data establish endogenous expression of CD80 and CD86 by activated T cells is not due to ligand capture by transendocytosis and highlight clear differences in their expression patterns and associated functions.

Highlights

The activation of CD4+ T cells is dependent upon two signals provided by antigen presenting cells (APCs)
It is well established that CD80 and CD86 expressed on antigen presenting cells play a role in providing costimulation to T cells via ligation of CD28 [4, 5, 36]
Both ligands can bind to the inhibitory receptor CTLA-4, which plays an important role in regulating T cell responses

Summary

Introduction

The activation of CD4+ T cells is dependent upon two signals provided by antigen presenting cells (APCs). In response to inflammatory signals, APCs upregulate the costimulatory ligands CD80 and CD86, which interact with the CD28 receptor expressed on T cells. This costimulatory “second signal” lowers the threshold of T cell activation [1], promotes T cell survival [2] and enhances production of cytokines [3], the T cell growth factor IL-2 [4, 5]. Since both CD28 and CTLA-4 can promote transfer of ligands to T cells it is not yet established whether CD80 and CD86 are intrinsically expressed by T cells or are acquired from APCs [10, 17,18,19]

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Results

Conclusion