Selective and nonselective stages in homing of T lymphocytes to the central nervous system during experimental allergic encephalomyelitis.
The diversity of Ag-specific receptors on T cells homing to an inflammatory infiltrate in the central nervous system has been analyzed. Experimental autoimmune encephalomyelitis, a T cell-mediated inflammatory disease of the central nervous system, was induced in Lewis rats with a CD4+, CD8- T cell line specific for peptide 68-86 of myelin basic protein. Within the line a wide array of TCR V beta genes was transcribed including the V beta 8, V beta 10, V beta 15, V beta 16, and V beta 19 families. Accumulation of T cells at the site of inflammation was determined by using RNA-polymerase chain reaction amplification of rearranged TCR V beta transcripts derived from brain. By 8 to 10 h after i.p. infusion of the pathogenic T cell line, TCR V beta transcripts, including mainly V beta families that were predominantly rearranged by the line, could be identified in brains. Restricted TCR V gene transcripts with predominance of the V beta 8 family were identified in brain 48 h after injection, before onset of disease. Paralysis was apparent by 4 to 5 days after injection. At this time diverse V beta gene transcripts were detected in brain, reaching a maximum by day 9, when paralyzed rats have recovered. By day 14 a second stage of limited heterogeneity in the T cell infiltrate could be identified with predominant expression of V beta 8, V beta 9, V beta 10, and V beta 19. Interestingly, three out of these four V beta families were predominantly expressed within the encephalitogenic line. Thus, T cell migration to brain in experimental autoimmune encephalomyelitis is characterized by a rapid penetration of T cells followed by a selective trapping of T cells before the clinical manifestations of disease. When clinical disease was present the T cell infiltrate was diverse, whereas in the post-acute phase of disease the T cells in the central nervous system had limited heterogeneity with selective accumulation of T cells transcribing the same V regions that were detected in the line that incited disease.
Karin
N
N
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, CA 94305-5235.
Szafer
F
F
Mitchell
D
D
Gold
D P
DP
Steinman
L
L
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000276:immunology*; D002465:Cell Movement; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D008969:Molecular Sequence Data; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
D016693:Receptors, Antigen, T-Cell, alpha-beta