Kinetics of T cell response in the testes and CNS during experimental autoimmune encephalomyelitis: Simultaneous blood-brain and -testis barrier permeability?

Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are regarded as autoimmune diseases of the central nervous system (CNS).  The CNS, testes, and eyes are immune privileged sites.  It was initially presumed that ocular involvement in EAE and infertility in MS are neural-mediated.  However, inflammatory molecules have been detected in the eyes of animals affected by EAE.  It prompted us to investigate if the testes may also be targeted by immune response during EAE. kinetics of T cell response was investigated in the CNS and testes in EAE at different clinical scores.  IFN-γ, IL-4, IL-17, and FoxP3 mRNA expressions were considered as representatives of Th1, Th2, Th17, and Treg, respectively. In CNS, IL-17 and IFN-γ were initially up-regulated and attenuated at the late phase of the disease.  IL-4 and FoxP3 were markedly down-regulated, but IL-4 was then up-regulated at the late phase of the disease.  In the testes, IFN-γ and IL-17 were diminished but increased at the late phase of the disease.  FoxP3 was gradually increased from the initial step to the peak of the disease.  IL-17/ IFN-γ showed a similar pattern between the CNS and testes.  However, FoxP3 and IL-4 expression appeared to have different timing patterns in the CNS and testes. Given the permeability in blood-retina/brain/CSF barrier by complete Freund’s adjuvant, the pattern of T cells may be changed in the testes during EAE as a consequence of the blood-testis barrier permeability. More research is required to explore the connection between immune privileged organs.