OX-40 antibody enhances for autoantigen specific V beta 8.2+ T cells within the spinal cord of Lewis rats with autoimmune encephalomyelitis.
The V beta 8.2 T cell receptor (TCR) component is the predominant V beta gene product associated with antigen specific CD4+ T cell response to the major encephalitogenic epitope of myelin basic protein (MBP) in Lewis rats. Lewis rats were actively immunized with MBP in complete Freund's adjuvant and the V beta 8.2 positive and negative cells were analyzed for IFN-gamma mRNA production and OX-40 cell surface expression during the onset of EAE. The V beta 8.2+ T cells isolated from the spinal cord produced the majority of mRNA for IFN-gamma and also showed a marked enhancement for OX-40 expression compared to V beta 8.2+ T cells isolated from the lymph nodes. Only a fraction of IL-2 receptor positive T cells examined ex vivo from the inflammatory compartments co-expressed the OX-40 antigen. These results suggested that OX-40 cell surface expression could be used to identify and isolate the most recently activated T cells ex vivo. OX-40+ T cells isolated from the spinal cord were highly enriched for the V beta 8.2 T cell receptor component compared to OX-40- or unsorted spinal cord lymphocytes. OX-40+ T cells isolated from the spinal cord had an enhanced response to MBP, whereas OX-40+ cells isolated from the lymph nodes responded to both MBP and purified protein derivative. These data suggest that activated T cells can be isolated and characterized with the OX-40 antibody which only respond to the antigens present at the local site. The data also imply that isolation of OX-40+ T cells will be useful in identifying V beta biases and autoantigen specific cells within inflamed tissues even when the antigen specificity is unknown.
Weinberg
A D
AD
Department of Neuroimmunology, Veteran Affairs Medical Center, Portland, OR 97201, USA.
Lemon
M
M
Jones
A J
AJ
Vainiene
M
M
Celnik
B
B
Buenafe
A C
AC
Culbertson
N
N
Bakke
A
A
Vandenbark
A A
AA
Offner
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000473:pathology; D015551:Autoimmunity; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D002469:Cell Separation; D002555:Cerebrospinal Fluid / Q000166:cytology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000473:pathology; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology / Q000633:toxicity; D016133:Polymerase Chain Reaction; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001324:Autoantigens; D004676:Myelin Basic Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505718:Tnfrsf4 protein, rat; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D007371:Interferon-gamma