Target organ-specific up-regulation of the MRC OX-40 marker and selective production of Th1 lymphokine mRNA by encephalitogenic T helper cells isolated from the spinal cord of rats with experimental autoimmune encephalomyelitis.
Lewis x Buffalo F1 rat lymphocytes express both forms of the allelic marker RT7.1 (Lewis) and RT7.2 (Buffalo). We generated myelin basic protein (MBP)-specific encephalitogenic F1 T helper cell lines and adoptively transferred them into naive irradiated Lewis recipients, which enabled us to detect and isolate donor T cells (with RT7.2) within the recipients. The spinal cord and cerebrospinal fluid (CSF) were highly enriched for the donor T cells compared with the blood and spleen. The donor cell number peaked on the first day of disease in the spinal cord and CSF and decreased as the disease progressed. A high percentage of the donor T cells isolated from the spinal cord were positive for the T helper cell activation marker OX-40, whereas a (lower) percentage of CSF donor cells expressed OX-40. Donor cells isolated from blood or spleen were negative for OX-40 expression. In contrast, the IL-2 receptor (CD25) was positive on all the transferred T cells in all tissue sites examined. Cell-sorting experiments showed that the MBP-specific donor cells were enriched for IFN-gamma, IL-2, TNF-alpha, and IL-3 mRNA when compared with the host-recruited spinal cord cells, whereas similar amounts of IL-10 mRNA were produced by both populations. Lymphokine mRNA production was also enriched in donor T cells isolated from the spinal cord compared with donor T cells isolated from the spleen. The spinal cord donor cells produced higher levels of IL-2, IFN-gamma, and IL-3 mRNA, whereas similar amounts of IL-10 and TNF-alpha mRNA were produced from donor cells isolated from the spleen and the spinal cord. Our data suggest that the amount/percentage, activation state, and enhanced lymphokine production at the site of inflammation are all important factors in determining the autoimmune potential of Ag-specific effector T helper cells.
Weinberg
A D
AD
Department of Neuroimmunology 151-D, VA Medical Center/Research, Portland, OR 97201.
Wallin
J J
JJ
Jones
R E
RE
Sullivan
T J
TJ
Bourdette
D N
DN
Vandenbark
A A
AA
Offner
H
H
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011915:Rats, Inbred BUF; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000276:immunology; D013154:Spleen / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D015854:Up-Regulation
D000945:Antigens, Differentiation, T-Lymphocyte; D017931:DNA Primers; D008222:Lymphokines; D008565:Membrane Proteins; D004676:Myelin Basic Protein; D012333:RNA, Messenger