Activated/effector CD4+ T cells exacerbate acute damage in the central nervous system following traumatic injury. J Neuroimmunol 2003 Mar;136(1-2):54-66
Date
03/07/2003Pubmed ID
12620643DOI
10.1016/s0165-5728(03)00008-0Scopus ID
2-s2.0-0037333903 (requires institutional sign-in at Scopus site) 92 CitationsAbstract
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.
Author List
Fee D, Crumbaugh A, Jacques T, Herdrich B, Sewell D, Auerbach D, Piaskowski S, Hart MN, Sandor M, Fabry ZAuthor
Dominic B. Fee MD Vice Chair, Professor in the Neurology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adoptive TransferAnimals
Apoptosis
Brain
Brain Injuries
CD4-Positive T-Lymphocytes
Female
Homeodomain Proteins
Hyaluronan Receptors
Immunosuppressive Agents
Inflammation
L-Selectin
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Mice, Knockout
Nerve Degeneration
Spinal Cord Injuries