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Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS) that can be induced in susceptible mice by the transfer of autoreactive T cells that recognize myelin basic protein (MBP). The onset and subsequent recovery from disease are associated with distinct patterns of cytokine and chemokine expression within the inflammatory lesions of the CNS. Given the likely importance of the local cytokine milieu in regulating the disease process, it would be preferable to administer cytokines locally to the CNS and reduce systemic delivery in order to evaluate their immunoregulatory roles in EAE. For this purpose, we have used retrovirally transduced T cells from MBP-specific T cell receptor transgenic mice in an attempt to target cytokine delivery to the CNS where MBP is primarily expressed. We have found that T cells expressing granulocyte macrophage colony-stimulating factor (GM-CSF) induce severe, chronic EAE from which mice fail to recover. Our results indicate that increased local GM-CSF expression could play an important role in inducing chronic EAE. [Copyright &y& Elsevier]

IFNα/β, IL-12, and IL-15 regulate NK cell activation and expansion, but signals triggering resolution of the NK response upon induction of adaptive immunity remain to be defined. We now report that IL-21, a product of activated T cells, may serve this function. Mice lacking IL-21R (IL-21R−/−) had normal NK cell development but no detectable responses to IL-21. IL-21 enhanced cytotoxic activity and IFNγ production by activated murine NK cells but did not support their viability, thus limiting their duration of activation. Furthermore, IL-21 blocked IL-15-induced expansion of resting NK cells, thus preventing the initiation of further innate responses. In contrast, IL-21 enhanced the proliferation, IFNγ production, and cytotoxic function of CD8+ effector T cells in an allogeneic MLR. These observations suggest that IL-21 promotes the transition between innate and adaptive immunity. [Copyright &y& Elsevier]