Myelin basic protein-specific T lymphocytes induce chronic relapsing experimental autoimmune encephalomyelitis in lymphocyte-deficient (SCID) mice.
Myelin basic protein (BP)-specific T lymphocyte cell lines were selected from the lymph nodes (LN) of BP-immunized, H-2d, CXJ-1 mice prior to the onset of clinical disease. These CD4+ T cells induced severe acute experimental autoimmune encephalomyelitis (EAE) in MHC-compatible (H-2d), lymphocyte-deficient (SCID) mice (C.B-17scid/scid). The incidence of disease was much higher in immunodeficient SCID mice (71%) than in syngeneic immunocompetent CXJ-1 mice (5%). SCID mice with EAE had an acute progressive paralytic disease with inflammation and myelin loss detected in the spinal cord. Eighty-six percent (12/14) of mice followed for more than 2 weeks had 1 or more relapses of EAE. These results demonstrate that clinical remission and relapse of EAE can be induced by the single adoptive transfer of a LN-derived BP-specific T cell line in the absence of host-derived effector and regulatory lymphocytes. Furthermore, the data demonstrate that the pathogenic potential of BP-specific T cells is greater in lymphocyte-deficient SCID mice compared with immunocompetent mice, suggesting that autoreactive T cells are controlled by potent inhibitory mechanisms associated with regulatory lymphocytes. These results are relevant to mechanisms of disease remission and relapse mediated by lymphocytes involved in paralytic inflammatory diseases such as multiple sclerosis (MS).
Jones
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Research Service, VA Medical Center, Portland, OR 97201, USA. jonesric@ohsu.edu
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Bourdette
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D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002460:Cell Line; D017690:Cell Transplantation; D002908:Chronic Disease; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D000939:Epitopes; D005260:Female; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000032:analysis; D016177:Macrophage-1 Antigen / Q000032:analysis; D051379:Mice; D016513:Mice, SCID / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*; D012008:Recurrence; D013116:Spinal Cord / Q000737:chemistry / Q000276:immunology; D014611:Vaccination
D000939:Epitopes; D016177:Macrophage-1 Antigen; D004676:Myelin Basic Protein; D017493:Leukocyte Common Antigens