Microglial major histocompatibility complex glycoprotein-1 in the axotomized facial motor nucleus: Regulation and role of tumor necrosis factor receptors 1 and 2

• Published in: Journal of comparative neurology (1911) Vol. 470; no. 4; pp. 382 - 399
• Main Authors: Bohatschek, M., Kloss, C.U.A., Hristova, M., Pfeffer, K., Raivich, G.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.03.2004
• Subjects: Animals; Antigens, CD - genetics; Antigens, CD - physiology; Axotomy; facial motor nucleus; Facial Nerve - chemistry; Facial Nerve - physiology; Glycoproteins - antagonists & inhibitors; Glycoproteins - biosynthesis; Histocompatibility Antigens Class I - biosynthesis; Histocompatibility Antigens Class I - metabolism; MHC1; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Mice, SCID; Microglia - chemistry; Microglia - physiology; Receptors, Tumor Necrosis Factor - deficiency; Receptors, Tumor Necrosis Factor - genetics; Receptors, Tumor Necrosis Factor - physiology; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; scid; tumor necrosis factor receptors 1 and 2
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/cne.20017

Presentation of antigen is key to the development of the immune response, mediated by association of antigen with major histocompatibility complex glycoproteins abbreviated as MHC1 and MHC2. In the current study, we examined the regulation of MHC1 in the brain after facial axotomy. The normal facial motor nucleus showed no immunoreactivity for MHC1 (MHC1‐IR). Transection of the facial nerve led to a strong and selective up‐regulation of MHC1‐IR on the microglia in the affected nucleus, beginning at day 2 and reaching a maximum 14 days after axotomy, coinciding with a peak influx of the T lymphocytes that express CD8, the lymphocyte coreceptor for MHC1. Specificity of the MHC1 staining was confirmed in β2‐microglobulin‐deficient mice, which lack normal cell surface MHC1‐IR. MHC1‐IR was particularly strong on phagocytic microglia, induced by delayed neuronal cell death, and correlated with the induction of mRNA for tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, and interferon‐γ and the influx of T lymphocytes. Mice with severe combined immunodeficiency (scid), lacking T and B cells, showed an increase in the number of MHC1‐positive nodules but no significant effect on overall MHC1‐IR. Transgenic deletion of the IL1 receptor type I, or the interferon‐γ receptor type 1 subunit, did not affect the microglial MHC1‐IR. However, a combined deletion of TNF receptors 1 and 2 (TNFR1&2‐KO) led to a decrease in microglial MHC1‐IR and to a striking absence of the phagocytic microglial nodules. Deletion of TNFR2 (p75) did not have an effect; deletion of TNFR1 (p55) reduced the diffuse microglial staining for MHC1‐IR but did not abolish the MHC1+ microglial nodules. In summary, neural injury leads to the induction of MHC1‐IR on the activated, phagocytic microglia. This induction of MHC1 precedes the interaction with the immune system, at least in the facial motor nucleus model. Finally, the impaired induction of these molecules, up to now, only in the TNFR‐deficient mice underscores the central role of TNF in the immune activation of the injured nervous system. J. Comp. Neurol. 470:382–399, 2004. © 2004 Wiley‐Liss, Inc.