Lymphokine mRNA expression in the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis is associated with a host recruited CD45R hi/CD4+ population during recovery.
To evaluate CD4+ T cell subpopulations involved in the induction and recovery from experimental autoimmune encephalomyelitis (EAE), the CD45R phenotype and lymphokine mRNA profile was evaluated for encephalitogenic CD4+ T cell lines in vitro and compared to CD4+ T cells isolated from the spinal cord of Lewis rats with EAE. All of the myelin basic protein (MBP)-specific T cell lines and clones that adoptively transferred EAE were > 90% CD4+ and > 90% CD45R lo. A time course of EAE disease progression was monitored as a function of the percentage of CD45R hi/CD4+ T cells isolated from the spinal cords of diseased animals. The majority of CD4+ T cells found in the central nervous system during the early phase of passive EAE were CD45R lo (the same as the encephalitogenic lines/clones). A large increase of the CD45R hi/CD4+ T cells (up to 45%) was observed during the peak and recovery phases of EAE. Lymphokine mRNA production was analyzed from antigen-stimulated MBP-specific lines, and from spinal cord lymphocytes isolated from rats with EAE. The BP-specific lines produced Th1 lymphokines (IL-2, IFN-gamma, and TNF-alpha), while the spinal cord lymphocytes produced the same Th1 lymphokines as well as IL-4 and IL-10. The CD45R hi/CD4+ T cells isolated from the spinal cords were larger and expressed more lymphokine RNA per cell than the CD45R lo/CD4+ T cells. The encephalitogenic cells (CD45R lo) were detected in the spinal cords of rats with a fluorescent dye and by allelic transfers and all of the CD45R hi/CD4+ T cells were found to be host recruited. Thus, it appears that the CD45R hi/CD4+ lymphocytes found in the spinal cord represent a host-recruited, activated cellular infiltrate that increased in number in the recovery phase of EAE and synthesized both Th1 and Th2 lymphokines.
Weinberg
A D
AD
Veteran Affairs Medical Center, Department of Neuroimmunology 151-D, Portland, OR 97201.
Wyrick
G
G
Celnik
B
B
Vainiene
M
M
Bakke
A
A
Offner
H
H
Vandenbark
A A
AA
D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D017493:Leukocyte Common Antigens / Q000032:analysis*; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D051381:Rats; D011915:Rats, Inbred BUF; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000378:metabolism*
D008222:Lymphokines; D004676:Myelin Basic Protein; D012333:RNA, Messenger; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D017493:Leukocyte Common Antigens