title: Activated/effector CD4+ T cells exacerbate acute damage in the central nervous system following traumatic injury.
abstract: CD4(+) helper T cells (Th) have been demonstrated to participate in the chronic phase of traumatic injury repair in the central nervous system (CNS). Here, we show that CD4(+) T cells can also contribute to the severity of the acute phase of CNS traumatic injury. We compared the area of tissue damage and the level of cellular apoptosis in aseptic cerebral injury (ACI) sites of C57BL/6 wild type and RAG1(-/-) immunodeficient mice. We demonstrate that ACI is attenuated in RAG1(-/-) mice compared to C57BL/6 animals. Adoptive transfer of CD4(+)CD62L(low)CD44(high) activated/effector T cells 24 h prior to ACI into RAG1(-/-) mice resulted in a significantly enhanced acute ACI that was comparable to ACI in the C57BL/6 animals. Adoptive transfer of CD4(+)CD62L(high)CD44(low) naive/non-activated T cells did not increase ACI in the brains of RAG1(-/-) mice. T cell inhibitory agents, cyclosporin A (CsA) and FK506, significantly decreased ACI-induced acute damage in C57BL/6 mice. These results suggest a previously undescribed role for activated/effector CD4(+) T cells in exacerbating ACI-induced acute damage in the CNS and raise a novel possibility for acute treatment of sterile traumatic brain injury.
authors.affiliation: Department of Neurology, University of Wisconsin-Madison, 53706, USA.
authors.forename: Dominic
authors.initials: D
authors.lastname: Fee
authors.forename: Amanda
authors.initials: A
authors.lastname: Crumbaugh
authors.forename: Thomas
authors.initials: T
authors.lastname: Jacques
authors.forename: Benjamin
authors.initials: B
authors.lastname: Herdrich
authors.forename: Diane
authors.initials: D
authors.lastname: Sewell
authors.forename: David
authors.initials: D
authors.lastname: Auerbach
authors.forename: Shari
authors.initials: S
authors.lastname: Piaskowski
authors.forename: Michael N
authors.initials: MN
authors.lastname: Hart
authors.forename: Matyas
authors.initials: M
authors.lastname: Sandor
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Fabry
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D019041:L-Selectin / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D013119:Spinal Cord Injuries / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy
chemical_list: D018398:Homeodomain Proteins; D018960:Hyaluronan Receptors; D007166:Immunosuppressive Agents; D019041:L-Selectin; C064658:RAG-1 protein