title: Traumatic brain injury causes selective, CD74-dependent peripheral lymphocyte activation that exacerbates neurodegeneration.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  Taken together, the data support the hypothesis that neurodegeneration following TBI is dependent upon antigen processing and presentation that requires CD74.
authors.affiliation: Department of Surgery, Texas A&M University Health Science Center, Temple, TX, USA. tobin@medicine.tamhsc.edu.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Tobin
authors.affiliation: Department of Surgery, Texas A&M University Health Science Center, Temple, TX, USA. mukerjeesanjib@gmail.com.|Central Texas Veterans Health Care System, Temple, TX, USA. mukerjeesanjib@gmail.com.
authors.forename: Sanjib
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Department of Surgery, Texas A&M University Health Science Center, Temple, TX, USA. jkain@medicine.tamhsc.edu.|Central Texas Veterans Health Care System, Temple, TX, USA. jkain@medicine.tamhsc.edu.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Kain
authors.affiliation: Department of Anthropology, University of Texas, Austin, TX, USA. suekrogers3@gmail.com.
authors.forename: Susannah K
authors.initials: SK
authors.lastname: Rogers
authors.affiliation: Department of Surgery, Baylor Scott and White Health, Temple, TX, USA. shenderson@sw.org.
authors.forename: Stephanie K
authors.initials: SK
authors.lastname: Henderson
authors.affiliation: Department of Surgery, Texas A&M University Health Science Center, Temple, TX, USA. motal@medicine.tamhsc.edu.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Motal
authors.affiliation: Department of Surgery, Texas A&M University Health Science Center, Temple, TX, USA. newellrogers@tamhsc.edu.|Department of Surgery, Baylor Scott and White Health, Temple, TX, USA. newellrogers@tamhsc.edu.|Texas A&M Health Science Center, Baylor Scott and White Health, 702 SW. HK Dodgen Loop, MRB. Rm. 114B, Temple, TX, 76504, USA. newellrogers@tamhsc.edu.
authors.forename: M Karen
authors.initials: MK
authors.lastname: Newell Rogers
authors.affiliation: Department of Surgery, Texas A&M University Health Science Center, Temple, TX, USA. lshapiro@medicine.tamhsc.edu.|Central Texas Veterans Health Care System, Temple, TX, USA. lshapiro@medicine.tamhsc.edu.|Department of Surgery, Baylor Scott and White Health, Temple, TX, USA. lshapiro@medicine.tamhsc.edu.
authors.forename: Lee A
authors.initials: LA
authors.lastname: Shapiro
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000502:physiology; D001921:Brain / Q000276:immunology*; D001930:Brain Injuries / Q000150:complications / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D007113:Immunity, Innate / Q000502:physiology; D008213:Lymphocyte Activation / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000276:immunology*; D015213:Neuroimmunomodulation / Q000502:physiology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; C045084:invariant chain