When RRMS patients develop irreversible and progressive deterioration of neurological functions with or without clinical relapses in the later stage of the disease, traditionally described as conversion to secondary progressive multiple sclerosis (SPMS) [1], the contribution of the peripheral immune system decreases, and the immune response is characterized by CNS-compartmentalized inflammation involving CD8+ T cells and plasma cells that survive and persist in the CNS and surrounding meninges, an microglial and astrocytic inflammatory response [6,7]. The gene discussed is CD8A; the disease is secondary progressive multiple sclerosis.