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 inflamm atory infiltrate in the central nervous system has been analyzed. Expe rimental 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 pr otein. Within the line a wide array of TCR Vbeta genes was transcribed including the Vbeta8, Vbeta10, Vbeta15, Vbeta16, and Vbeta19 families . Accumulation of T cells at the site of inflammation was determined b y using RNA-polymerase chain reaction amplification of rearranged TCR Vbeta transcripts derived from brain. By 8 to 1 0 h after i.p. infusio n of the pathogenic T cell line, TCR Vbeta transcripts, including main ly Vbeta families that were predominantly rearranged by the line, coul d be identified in brains. Restricted TCR V gene transcripts with pred ominance of the Vbeta8 family were identified in brain 48 h after inje ction, before onsetof disease. Paralysis was apparent by 4 to 5 days a fter injection. At this time diverse Vbeta gene transcripts were detec ted in brain, reaching a maximum by day 9, when paralyzed rats have re covered. By day 14 a second stage of limited heterogeneity in the T ce ll infiltrate could be identified with predominant expression of Vbeta 8, Vbeta9, Vbeta10, and Vbeta19. Interestingly, three out of these fou r Vbeta families were predominantly expressed within the encephalitoge nic line. Thus, T cell migration to brain in experimental autoimmune e ncephalomyelitis is characterized by a rapid penetration of T cells fo llowed by a selective trapping of T cells before the clinical manifest ations of disease. When clinical disease was present the T cell infilt rate was diverse, whereas in the post-acute phase of disease the T cel ls in the central nervous system had limited heterogeneity with select ive accumulation of T cells transcribing the same V regions that were detected in the line that incited disease.