Presence of B‐7.2 (CD86) and lack of B7‐1 (CD80) on myelin‐phagocytosing MHC‐II positive rat microglia are associated with nondestructive immunity in vivo

Myelin‐associated epitopes are targets of destructive T‐cell responses during autoimmune diseases such as multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. However, autoimmune T cells do not respond in a destructive way to mechanically induced axonal degeneration despite myelin phagocytosis and presentation by local microglia. Using entorhinal cortex lesion, a model of axonal degeneration and reactive sprouting, we now show that myelin phagocytosing microglia up‐regulate MHC‐II and B7‐2 but lack expression of B7‐1, a costimulatory molecule related to destructive immunity. In zones of retrograde axonal degeneration, where axons undergo secondary damage and later contribute to the sprouting response, MHC‐II/B7‐2‐positive microglia are still found at 90 days postlesion. These cells exhibit the ramified morphology of resting microglia in the presence of CD4/B7‐2‐positive α/β T cells. Thus, in contrast to autoimmune brain disease, axonal degeneration lacks a signal to induce B7‐1 on microglial cells and the recruited T cells do not induce microglial activation. Differences in B7‐phenotype of local antigen presenting cells might provide an explanation for the important finding that autoimmune T cells elicit protective rather than destructive effects following axonal degeneration in the CNS.