Normal cerebrospinal fluid suppresses the in vitro development of cytotoxic T cells: role of the brain microenvironment in CNS immune regulation.
The regulatory role of cerebrospinal fluid (CSF) in brain physiology is well established, while our understanding of its role in brain immunity is undefined. We demonstrate that normal rat CSF suppresses the in vitro development of mastocytoma-specific CTL activity in restimulated splenocytes from Balb/c mice, a strain unable to reject this tumor from the brain. Suppression is dependent on TGF-beta, revealed by reversal of suppression with specific neutralizing antibody. In contrast, mice which can reject this tumor from the brain, such as Balb/c mice with immunological memory to the tumor or CD-1 mice with major histo-incompatibility with the tumor, have populations of precursor CTL which are resistant to CSF-induced suppression, in the in vitro restimulation protocol. We propose that the susceptibility to CSF-induced suppression of peripherally generated immune cells that traffic to the brain plays an important role in determining whether growing tumor cells survive in the brain.
Gordon
L B
LB
The Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912, USA.
Nolan
S C
SC
Ksander
B R
BR
Knopf
P M
PM
Harling-Berg
C J
CJ
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001921:Brain / Q000166:cytology*; D002460:Cell Line; D016922:Cellular Senescence / Q000502:physiology; D002490:Central Nervous System / Q000276:immunology*; D002555:Cerebrospinal Fluid / Q000502:physiology*; D005260:Female; D007107:Immune System / Q000502:physiology; D007156:Immunologic Memory / Q000502:physiology; D008415:Mastocytosis / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D051381:Rats; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000276:immunology
D000906:Antibodies; D016212:Transforming Growth Factor beta