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Open Access 01-12-2014 | Research

Traumatic brain injury causes selective, CD74-dependent peripheral lymphocyte activation that exacerbates neurodegeneration

Authors: Richard P Tobin, Sanjib Mukherjee, Jessica M Kain, Susannah K Rogers, Stephanie K Henderson, Heather L Motal, M Karen Newell Rogers, Lee A Shapiro

Published in: Acta Neuropathologica Communications | Issue 1/2014

Abstract

Introduction

Traumatic brain injury (TBI), a significant cause of death and disability, causes, as in any injury, an acute, innate immune response. A key component in the transition between innate and adaptive immunity is the processing and presentation of antigen by professional antigen presenting cells (APCs). Whether an adaptive immune response to brain injury is beneficial or detrimental is not known. Current efforts to understand the contribution of the immune system after TBI have focused on neuroinflammation and brain-infiltrating immune cells. Here, we characterize and target TBI-induced expansion of peripheral immune cells that may act as potential APCs. Because MHC Class II-associated invariant peptide (CLIP) is important for antigen processing and presentation, we engineered a competitive antagonist (CAP) for CLIP, and tested the hypothesis that peptide competition could reverse or prevent neurodegeneration after TBI.

Results

We show that after fluid percussion injury (FPI), peripheral splenic lymphocytes, including CD4+ and CD8+ T cells, regulatory T cells (Tregs), and γδ T cells, are increased in number within 24 hours after FPI. These increases were reversed by CAP treatment and this antagonism of CLIP also reduced neuroinflammation and neurodegeneration after TBI. Using a mouse deficient for the precursor of CLIP, CD74, we observed decreased peripheral lymphocyte activation, decreased neurodegeneration, and a significantly smaller lesion size following TBI.

Conclusion

Taken together, the data support the hypothesis that neurodegeneration following TBI is dependent upon antigen processing and presentation that requires CD74.

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Title: Traumatic brain injury causes selective, CD74-dependent peripheral lymphocyte activation that exacerbates neurodegeneration
Authors: Richard P Tobin
Sanjib Mukherjee
Jessica M Kain
Susannah K Rogers
Stephanie K Henderson
Heather L Motal
M Karen Newell Rogers
Lee A Shapiro
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Acta Neuropathologica Communications / Issue 1/2014
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/s40478-014-0143-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Traumatic brain injury causes selective, CD74-dependent peripheral lymphocyte activation that exacerbates neurodegeneration

Abstract

Introduction

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Results

Conclusion

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