Brain, Vol. 117, No. 6, 1323-1332, 1994
© 1994 Guarantors of Brain
research-article |
Multiple sclerosis Immunomodulatory effects of human astrocytes on T cells
1Department of Neuroimmunology, Max-Planck-Institute of Psychiatry Martinsried 2Department of Neurology, University of Munich Germany 3Department of Organ and System Pathophysiology, Istituto Superiore di Sanità Rome, Italy 4Human Immunology Department, DNAX Research Institute California, USA
Correspondence to:
Correspondence to: Reinhard Hohlfeld, Department of Neurology, Klinikum Großhadern, University of Munich, D-81366 Munich, Germany
Using a human culture system, we have previously shown that interferon-
-and tumour necrosis factor-
-stimulated astrocytes are capable of presenting antigens to T lymphocytes, but do not support antigen-dependent T cell proliferation. To gain further insight into the mechanisms involved in the local regulation of intracerebral T cell responses, we have investigated the effects of astrocytes on T cell proliferation induced by peripheral blood-derived mononuclear cells (PBMC). We found that astrocytes derived from human embryonic brain were able to suppress PBMC-dependent proliferation of antigen-specific, CD4+ T cell lines. Interferon- production by PBMC-stimulated T cells was also suppressed by astrocytes, and this inhibition was seen as early as 6 h after initiation of co-culture. The inhibitory effect was observed in the presence of both HLA matched and mismatched astrocytes and was mediated by astrocyte-derived soluble factor(s) rather than by direct cellular contact. Inhibition of T cell proliferation was incompletely reverted by indomethacin, suggesting that prostaglandins were partially involved in the suppressive effect. The cytotoxic mediator nitric oxide was not involved in astrocyte-mediated inhibition. These observations led us to further investigate the contribution of other mediators known to down-regulate inflammatory processes. Our astrocyte cultures did not synthesize interleukin (IL)-4 or IL-10, whereas they secreted both the latent and active forms of transforming growth factor- ß2. Transforming growth factor-ß was, however, found not to participate in astrocyte-induced inhibition in vitro. The inhibitory properties of human astrocytes may contribute to confinement of inflammatory lesions in multiple sclerosis and other inflammatory diseases of the central nervous system.
multiple sclerosis; astrocyte; T cell; autoimmunity; lesion
.
Received April 28, 1994. Revised July 12, 1994. Accepted July 30, 1994.
*Present address: Institut f
r Klinische und Molekulare Virologie, Universität Erlangen-Nrnberg, Erlangen, Germany
Present address: Department of Neurology, University of Gottingen, Germany
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