Activated/effector CD4+ T cells exacerbate acute damage in the central nervous system following traumatic injury.
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.
Fee
Dominic
D
Department of Neurology, University of Wisconsin-Madison, 53706, USA.
Crumbaugh
Amanda
A
Jacques
Thomas
T
Herdrich
Benjamin
B
Sewell
Diane
D
Auerbach
David
D
Piaskowski
Shari
S
Hart
Michael N
MN
Sandor
Matyas
M
Fabry
Zsuzsa
Z
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
D018398:Homeodomain Proteins; D018960:Hyaluronan Receptors; D007166:Immunosuppressive Agents; D019041:L-Selectin; C064658:RAG-1 protein