Figure 6.

Possible autoimmune mechanisms underlying paraneoplastic cerebellar degenerations. Naive CD4+ T cells are first sensitized by onconeural antigens (for example, Cdr2 or Hu) in the peripheral lymph nodes, and they differentiate into antigen-specific Th1 or ThFH cells. Activated CD8+ T cells are aggressive toward cells presenting these onconeural antigens through FasL receptor-mediated or perforin/ granzyme-mediated apoptosis. It is uncertain how CNS tolerance is broken down to develop cerebellar degenerations.