Role of astrocytes in antigen presentation and naive T-cell activation.
Astrocytes may have a role in antigen presentation in inflammatory diseases of the central nervous system (CNS) such as MS and EAE. In this study, we have assessed whether purified astrocyte cultures could stimulate naive CD4(+) or CD8(+) T-cells from TCR transgenic mice. As previously described, astrocytes sustained antigen-specific CD4(+) T-cell proliferation only in the presence of IFN-gamma, which promotes expression of both MHC class II and B7 molecules on astrocytes. In addition, we show that astrocytes also have the capacity to present antigens to naive CD8(+) T-cell and promote their proliferation. In one system, this CD8(+) T-cell proliferation was dependent on IFN-gamma-induced upregulation of B7 molecules on astrocytes. However, in a second TCR transgenic system, astrocytes could induce naive CD8(+) T-cell proliferation even in the absence of IFN-gamma. The possible implications of these findings for the pathophysiology of CNS inflammatory diseases are discussed.
Cornet
A
A
INSERM U 267, Paul Brousse Hospital, 14 avenue Paul Vaillant-Couturier, 94807, Villejuif, France.
Bettelli
E
E
Oukka
M
M
Cambouris
C
C
Avellana-Adalid
V
V
Kosmatopoulos
K
K
Liblau
R S
RS
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D015703:Antigens, CD / Q000502:physiology; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000502:physiology; D002478:Cells, Cultured; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*
D015703:Antigens, CD; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma