The potential of cells within the central nervous system (CNS) to initiate T lymphocyte responses is not known and was the subject of this study. Using the ability of virgin T lymphocytes to proliferate in a primary response to allogeneic determinants on antigen-presenting cells (APC), we have examined the capacity of major histocompatibility complex (MHC)-expressing astroglial cells to act as stimulators of primary and secondary T cell responses. Neither freshly isolated astrocytes nor primary astrocyte cultures pretreated with interferon gamma (IFN-gamma) to upregulate MHC class I and II expression stimulated unfractionated lymph node (LN) cell populations in the primary mixed lymphocyte reaction. In mixing experiments, astrocytes did not inhibit the T cell response to allogeneic LN stimulators. Purified responder CD4+ T cells also were not stimulated to proliferate or secrete interleukin 2 (IL-2) by MHC class I- and II-expressing astrocytes. In contrast to their inability to stimulate virgin, alloreactive CD4+ T cells, astrocytes were able to specifically stimulate an alloreactive CD4+ T cell line. Unprimed CD8+ T cells, however, exhibited some weak autonomous proliferation to astrocyte stimulators but this response was only substantial in the presence of exogenous IL-2, the latter predominantly being a CD4+ T cell product. Those CD8+ T cells responding in the presence of IL-2 were mainly T cell receptor alpha/beta+ IL-2 receptor (alpha chain)+, and a majority had shifted from high to low CD45R expression. Given the virtual dependence of CD8+ T cells in these studies, on CD4+ T cell help, and the complete absence of activation of this latter subset by astrocytes, it is clear that in the context of this resident CNS cell, further activation of either T cell subset by astrocytes within the CNS can only follow priming by another type of APC. The implications of these results for the induction of T cell responses in the CNS are discussed.
Article|
May 01 1991
Major histocompatibility complex-expressing nonhematopoietic astroglial cells prime only CD8+ T lymphocytes: astroglial cells as perpetuators but not initiators of CD4+ T cell responses in the central nervous system.
J D Sedgwick,
J D Sedgwick
Institute for Virology and Immunobiology, University of Würzburg, Germany.
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R Mössner,
R Mössner
Institute for Virology and Immunobiology, University of Würzburg, Germany.
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S Schwender,
S Schwender
Institute for Virology and Immunobiology, University of Würzburg, Germany.
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V ter Meulen
V ter Meulen
Institute for Virology and Immunobiology, University of Würzburg, Germany.
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J D Sedgwick
Institute for Virology and Immunobiology, University of Würzburg, Germany.
R Mössner
Institute for Virology and Immunobiology, University of Würzburg, Germany.
S Schwender
Institute for Virology and Immunobiology, University of Würzburg, Germany.
V ter Meulen
Institute for Virology and Immunobiology, University of Würzburg, Germany.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1991) 173 (5): 1235–1246.
Citation
J D Sedgwick, R Mössner, S Schwender, V ter Meulen; Major histocompatibility complex-expressing nonhematopoietic astroglial cells prime only CD8+ T lymphocytes: astroglial cells as perpetuators but not initiators of CD4+ T cell responses in the central nervous system.. J Exp Med 1 May 1991; 173 (5): 1235–1246. doi: https://doi.org/10.1084/jem.173.5.1235
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