The central nervous system environment controls effector CD4+ T cell cytokine profile in experimental allergic encephalomyelitis

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Abstract
In experimental allergic encephalomyelitis (EAE), CD4+ T cells infiltrate the central nervous system (CNS). We derived CD4+ T cell lines from SJL/J mice that were specific for encephalitogenic myelin basic protein (MBP) peptides and produced both Th1 and Th2 cytokines. These lines transferred EAE to naive mice. Peptide‐specific cells re‐isolated from the CNS only produced Th1 cytokines, whereas T cells in the lymph nodes produced both Th1 and Th2 cytokines. Mononuclear cells isolated from the CNS, the majority of which were microglia, presented antigen to and stimulated MBP‐specific T cell lines in vitro. Although CNS antigen‐presenting cells (APC) supported increased production of interferon (IFN)‐γ mRNA by these T cells, there was no increase in the interleukin (IL)‐4 signal, whereas splenic APC induced increases in both IFN‐γ and IL‐4. mRNA for IL‐12 (p40 subunit) was up‐regulated in both infiltrating macrophages and resident microglia from mice with EAE. We have thus shown that a Th1 cytokine bias within the CNS can be induced by CNS APC, and that IL‐12 is up‐regulated in microglial cells within the CNS of mice with EAE. Microglia may therefore control Th1 cytokine responses within the CNS.

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