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.
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.
Sedgwick
J D
JD
Institute for Virology and Immunobiology, University of Würzburg, Germany.
Mössner
R
R
Schwender
S
S
ter Meulen
V
V
D000818:Animals; D001253:Astrocytes / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D015704:CD4 Antigens / Q000276:immunology; D002490:Central Nervous System / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism / Q000502:physiology; D008285:Major Histocompatibility Complex / Q000276:immunology* / Q000502:physiology; D009457:Neuroglia / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000502:physiology*
D015704:CD4 Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D007371:Interferon-gamma