CD28 expression is required after T cell priming for helper T cell responses and protective immunity to infection

Author:

Linterman Michelle A12,Denton Alice E23,Divekar Devina P12,Zvetkova Ilona4,Kane Leanne5,Ferreira Cristina6,Veldhoen Marc6ORCID,Clare Simon5,Dougan Gordon5,Espéli Marion12,Smith Kenneth GC12

Affiliation:

1. Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom

2. Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom

3. Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom

4. University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom

5. Wellcome Trust Genome Campus, Wellcome Trust Sanger Institute, Cambridge, United Kingdom

6. Babraham Research Campus, Babraham Institute, Cambridge, United Kingdom

Abstract

The co-stimulatory molecule CD28 is essential for activation of helper T cells. Despite this critical role, it is not known whether CD28 has functions in maintaining T cell responses following activation. To determine the role for CD28 after T cell priming, we generated a strain of mice where CD28 is removed from CD4+ T cells after priming. We show that continued CD28 expression is important for effector CD4+ T cells following infection; maintained CD28 is required for the expansion of T helper type 1 cells, and for the differentiation and maintenance of T follicular helper cells during viral infection. Persistent CD28 is also required for clearance of the bacterium Citrobacter rodentium from the gastrointestinal tract. Together, this study demonstrates that CD28 persistence is required for helper T cell polarization in response to infection, describing a novel function for CD28 that is distinct from its role in T cell priming.

Funder

Wellcome Trust

Lister Institute of Preventive Medicine

National Health and Medical Research Council

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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