Traumatic brain injury causes selective, CD74-dependent peripheral lymphocyte activation that exacerbates neurodegeneration. Academic Article uri icon


  • 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 T cells, are increased in number within 24hours 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.

published proceedings

  • Acta Neuropathol Commun

altmetric score

  • 69.05

author list (cited authors)

  • Tobin, R. P., Mukherjee, S., Kain, J. M., Rogers, S. K., Henderson, S. K., Motal, H. L., Newell Rogers, M. K., & Shapiro, L. A.

citation count

  • 45

complete list of authors

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

publication date

  • January 2014