Characterization of CD4-CD8- T cell receptor alpha beta + T cells appearing in the subarachnoid space of rats with autoimmune encephalomyelitis.
Inflammation of the central nervous system (CNS) in experimental autoimmune encephalomyelitis (EAE) starts in the subarachnoid space (SAS) and spreads later to the adjacent CNS parenchyma. To characterize the nature of lesion-forming T cells in situ in more detail, T cells were isolated from the SAS and their surface phenotype and the nucleotide sequence of the junctional region of the T cell receptor (TCR) was determined and compared with those of the lymph node (LN) and spinal cord (SC) T cells. Characteristically, more than 70% of SAS TCR alpha beta + T cells isolated at the early stage of EAE lacked both CD4 and CD8 molecules, whereas those from LN and SC were either CD4+ or CD8+. Analysis of nucleotide sequences of the junctional region of TCR revealed that T cells bearing a sequence identical to that for encephalitogenic T cell clones were found in both SAS and SC. Furthermore, purified CD4-CD8- T cells expressed CD4 molecules after culture. At the same time, these T cells acquired reactivity to myelin basic protein and induced passive EAE in naive animals after adoptive transfer. Our results suggest that CD4-CD8- T cells in the SAS are precursors of lesion-forming T cells in the SC and that phenotype switching takes place during the process of T cell infiltration into the CNS parenchyma. The double-negative nature of these T cells may explain an escape of encephalitogenic T cells from negative selection in T cell differentiation.
Matsumoto
Y
Y
Department of Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan.
Abe
S
S
Tsuchida
M
M
Hirahara
H
H
Abo
T
T
Shin
T
T
Tanuma
N
N
Kojima
T
T
Ishihara
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013346:Subarachnoid Space / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D004676:Myelin Basic Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta