TABLE 2.

Contribution of the adaptive immune system in neurodegeneration and regeneration secondary to other pathology.

Secondary neurodegenerative diseases	Neurodegeneration	Regeneration
Multiple sclerosis	T cell depleted mice do not develop EAE (Ortiz-ortiz and Weigle, 1976). Adoptive transfer of MBP-specific CD4+T cells induce EAE (Pettinelli and McFarlin, 1981; Zamvil et al., 1985). Adoptive transfer of Th1 and Th17 cells induce classical and atypical EAE (Jager et al., 2009; Domingues et al., 2010).	Mice deficient in CD4+ or CD8+ T cells show impaired remyelination following lysolecithin-induced demyelination (Bieber et al., 2003). Tregs promote OPC differentiation and efficient remyelination (Dombrowski et al., 2017).
Stroke	Rag1 KO and SCID mice show a reduced infarct size after MCAO (Hurn et al., 2007; Kleinschnitz et al., 2010). Adoptive transfer of CD8 T cells into Rag1 KO mice increases infarct size (Mracsko et al., 2014). Specific antibody-mediated depletion of either CD4+ or CD8+ T cells decreased infarct size (Liesz et al., 2011). B lymphocytes mediate a delayed cognitive impairment following stroke in mice (Doyle et al., 2015).	Tregs accumulate following ischaemia and have a role in suppressing astrogliosis and promoting neurological recovery (Ito et al., 2019). Administration of CD34+ immune progenitor cells promoted revascularisation and neurogenesis (Taguchi et al., 2004).
Traumatic CNS injury	In SCI: SCID mice show better functional recovery after SCI (Luo et al., 2019). Rag2 KO mice, BCKO mice, Athymic nude rats and B cell depletion show less degeneration and improved recover (Potas et al., 2006; Ankeny et al., 2009; Wu et al., 2012; Casili et al., 2016). MBP-reactive lymphocytes contribute to SCI neurodegeneration (Jones et al., 2002). Antibodies against CXCL10 ameliorate SCI (Gonzalez et al., 2003). Rag1 KO mice administered with IgM antibodies show exacerbated pathology (Narang et al., 2017). CD8+ T cells inhibit neurite outgrowth in vitro (Pool et al., 2012). In TBI: Rag1–/– mice have a similar injury extent to controls in the closed head injury model (Weckbach et al., 2012). Inhibition of antigen processing/presentation reduces lesion size in a fluid percussion trauma model (Tobin et al., 2014).	In SCI: CD4 T cells promote neurite outgrowth in vitro (Pool et al., 2012). Adoptive transfer of Th1 cells promotes locomotor recovery in SCI (Ishii et al., 2012). Adoptive transfer of CD4+ T cells into IL-4 deficient mice promotes neuronal survival and regeneration (Walsh et al., 2015). Active immunization with MBP or transfer of MBP-T cells enhance SCI locomotor recovery and regeneration (Hauben et al., 2000). Myelin and spinal cord homogenate immunization improves regeneration and recovery (Huang et al., 1999; Sicotte et al., 2003). In TBI: Vaccination with Cop-1 (a synthetic mimic of MBP epitopes) reduced neuronal loss and promoted recovery (Kipnis et al., 2003).