Immunodeficiency impairs re-injury induced reversal of neuronal atrophy: relation to T cell subsets and microglia.
Following facial nerve resection in the mouse, a substantial number of neurons reside in an atrophied state (characterized by cell shrinkage and decreased ability to uptake Nissl stain), which can be reversed by re-injury. The mechanisms mediating the reversal of neuronal atrophy remain unclear. Although T cells have been shown to prevent neuronal loss following peripheral nerve injury, it was unknown whether T cells play a role in mediating the reversal of axotomy-induced neuronal atrophy. Thus, we used a facial nerve re-injury model to test the hypothesis that the reversal of neuronal atrophy would be impaired in recombinase activating gene-2 knockout (RAG-2 KO) mice, which lack functional T and B cells. Measures of neuronal survival were compared in the injured facial motor nucleus (FMN) of RAG-2 KO and wild-type (WT) mice that received a resection of the right facial nerve followed by re-injury of the same nerve 10 weeks later ("chronic resection+re-injury") or a resection of the right facial nerve followed by sham re-injury of the same nerve 10 weeks later ("chronic resection+sham"). We recently demonstrated that prior exposure to neuronal injury elicited a marked increase in T cell trafficking indicative of a T cell memory response when the contralateral FMN was injured later in adulthood. We examined if such a T cell memory response would also occur in the current re-injury model. RAG-2 KO mice showed no reversal of neuronal atrophy whereas WT mice showed a robust response. The reversal of atrophy in WT mice was not accompanied by a T cell memory response. Although the number of CD4(+) and CD8(+) T cells in the injured FMN did not differ from each other, double-negative T cells appear to be recruited in response to neuronal injury. Re-injury did not result in increased expression of MHC2 by microglia. Our findings suggest that T cells may be involved in reversing the axotomy-induced atrophy of injured neurons.
Ha
Grace K
GK
Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
Huang
Zhi
Z
Parikh
Ravi
R
Pastrana
Marlon
M
Petitto
John M
JM
D000818:Animals; D001284:Atrophy; D019771:Axotomy; D004268:DNA-Binding Proteins / Q000172:deficiency; D005154:Facial Nerve / Q000601:surgery; D020220:Facial Nerve Injuries / Q000150:complications* / Q000276:immunology / Q000473:pathology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007153:Immunologic Deficiency Syndromes / Q000150:complications*; D007156:Immunologic Memory; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D011149:Pons / Q000473:pathology*; D011184:Postoperative Period; D012086:Reoperation; D016176:T-Lymphocyte Subsets / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology; D014950:Wounds, Penetrating / Q000150:complications / Q000276:immunology / Q000473:pathology*
D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; C499308:Rag2 protein, mouse