title: Inhibition of antigen-stimulated effector T cells by human cerebrospinal fluid.
abstract: The brain is an immune-privilege site. To understand the mechanism of immune privilege in the brain, human cerebrospinal fluid (CSF) was examined for characteristics associated with fluids derived from other immune-privileged tissues. We first assayed for CSF suppression of effector T cell inflammatory activities. Primed T cells were activated with antigen and antigen-presenting cells in the presence of normal human or rabbit CSF, and T cell proliferation and interferon-gamma production were assayed. Human and rabbit CSF enhanced antigen-stimulated lymph node T cell proliferation and human CSF suppressed IFN-gamma production. T cell proliferation was suppressed by a low molecular weight (< 5 kDA) fraction of CSF and by transiently acidified unfractionated CSF. Normal CSF, similar to fluids from other immune-privileged sites, has the capacity to suppress production of proinflammatory lymphokines by antigen-stimulated effector T cells. Normal CSF also contains factors that have the potential to suppress effector T cell proliferation. Human CSF was assayed for factors known to mediate immunosuppression in other immune-privileged sites. Human CSF contained the immunosuppressive cytokine-transforming growth factor-beta (1.7 +/- 0.6 ng/ml), and the immunosuppressive neuropeptides alpha-melanocyte stimulating hormone (60 +/- 11 pg/ml), and vasoactive intestinal peptide (42 +/- 3 ng/ml). Much as fluids from other immune-privileged sites, CSF contains immunosuppressive cytokines that prevent activation of inflammatory-mediating (delayed-typed hypersensitivity) T cells. This suggests that, similar to other immune-privileged sites, cytokines and neuropeptides mediate immunosuppression in the brain.
authors.affiliation: Schepens Eye Research Institute, Boston, MA 02114, USA.
authors.forename: A W
authors.initials: AW
authors.lastname: Taylor
authors.forename: J W
authors.initials: JW
authors.lastname: Streilein
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D001921:Brain / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D002555:Cerebrospinal Fluid / Q000276:immunology*; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis / Q000494:pharmacology*; D016207:Cytokines / Q000032:analysis / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000276:immunology; D015213:Neuroimmunomodulation; D011817:Rabbits; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000134:cerebrospinal fluid / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000134:cerebrospinal fluid / Q000494:pharmacology; D000521:alpha-MSH / Q000134:cerebrospinal fluid / Q000494:pharmacology
chemical_list: D000942:Antigens, Bacterial; D002556:Cerebrospinal Fluid Proteins; D016207:Cytokines; D016212:Transforming Growth Factor beta; D014660:Vasoactive Intestinal Peptide; D000521:alpha-MSH; D007371:Interferon-gamma