ASTROCYTE CYTOLYSIS BY MHC CLASS II-SPECIFIC MOUSE T CELL CLONES
| Autor: | Christopher D. Lascola, Scott A. Flanders, Davide Maimone, Mark A. Jensen, Demetrios D. Skias, Anthony T. Reder, Dave W. Lancki |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cytotoxicity Immunologic Receptors Antigen T-Cell CD1 chemical and pharmacologic phenomena MHC class II antigen Epitopes Interferon-gamma Mice Pregnancy MHC class I Animals Cytotoxic T cell Transplantation MHC class II MHC Class I Protein biology Antigen processing Histocompatibility Antigens Class II Antibodies Monoclonal MHC restriction Flow Cytometry Intercellular Adhesion Molecule-1 Lymphocyte Function-Associated Antigen-1 Recombinant Proteins Clone Cells Cell biology Microscopy Fluorescence Mice Inbred DBA Astrocytes Immunology biology.protein Female Cell Adhesion Molecules |
| Zdroj: | Transplantation. 56:393-398 |
| ISSN: | 0041-1337 |
| DOI: | 10.1097/00007890-199308000-00028 |
| Popis: | The brain is "immunologically privileged," in part because class I and II MHC antigens are not normally present on glia or neurons. However, under certain conditions such as transplantation, glial cells express MHC proteins at levels sufficient for glia to become targets of immune responses. Cultured astrocytes expressing very low levels of MHC class I protein are killed efficiently by MHC class I antigen-specific CTL. Mouse brain allografts, however, are rejected by CD4+ T cells that are likely to be class II MHC-specific. The level of expression of MHC class II antigen needed to trigger specific killing of astrocytes by CD4+ T cells, independent of exogenous antigen, has not been studied. We examined the role of glial class II MHC in the lysis of cultured neonatal mouse astrocytes by an alloreactive murine CD4+ CTL alone. IFN-gamma induced functionally relevant increases in MHC class II antigen on target cells. Astrocytes were lysed by the CD4+ clone only when class II MHC antigens reached levels readily detectable by flow cytometry. MHC class II expression and lysis increased when astrocytes were coincubated with IFN-gamma and TNF-alpha. Conversely, lysis decreased when class II expression was downregulated by IFN-alpha/beta or dbcAMP. Cytolysis by CD4+ clones was blocked by antibodies to CD4 and LFA-1 on T cells, and to ICAM-1 and class II molecules on astrocytes. The role of LFA-1 in CD4+ cell-mediated lysis was greater than that of LFA-1/ICAM-1 in CD8+ T cell-mediated lysis. CD4+ cells may lyse activated astrocytes when the immune privilege of the brain is compromised as in transplantation, tumors, and inflammatory diseases. |
| Databáze: | OpenAIRE |
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