AlphaB-crystallin-reactive T cells from knockout mice are not encephalitogenic.
Alpha B-crystallin (alphaB) is a small heat shock protein that is strongly up-regulated in multiple sclerosis (MS) brain tissue, and can induce strong T cell responses. Assessing a potential encephalitogenic function for alphaB protein in MS and experimental autoimmune encephalomyelitis (EAE) has been challenging due to its ubiquitous expression that likely maintains central and peripheral tolerance to this protein in mice. To address this issue, we obtained alphaB-knockout (alphaB-KO) mice in H-2b background that lack immune tolerance to alphaB protein, and thus are capable of developing alphaB-specific T cells that could be tested for encephalitogenic activity after transfer into alphaB-expressing wild type (WT) mice. We found that T cell lines from spleens of alphaB protein-immunized alphaB-KO mice proliferated strongly to alphaB protein itself, and the majority of T cells were CD4+ and capable of secreting pro-inflammatory Th1 cytokines upon restimulation. However, transfer of such alphaB-reactive T cells back into WT recipients was not sufficient to induce EAE, compared to the transfer of mouse MOG-35-55 peptide-reactive T cells from the same donors that induced severe EAE in recipients. Moreover, alphaB-specific T cells failed to augment severity of actively induced EAE in WT mice that were expressing high levels of alphaB message in the CNS at the time of transfer. These results suggest that alphaB-specific T cells are immunocompetent but not encephalitogenic in 129SvEv mice, and that immune tolerance may not be the main factor that limits the encephalitogenic potential of alphaB.
Wang
Chunhe
C
Neuroimmunology Research, Veterans Affairs Medical Center, Portland, 97239, and Department of Neurology, Oregon Health and Science University, USA. wangch@ohsu.edu
Chou
Yuan K
YK
Rich
Cathleen M
CM
Link
Jason M
JM
Afentoulis
Michael E
ME
van Noort
Johannes M
JM
Wawrousek
Eric F
EF
Offner
Halina
H
Vandenbark
Arthur A
AA
D000595:Amino Acid Sequence; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D038203:alpha-Crystallin B Chain / Q000235:genetics / Q000276:immunology* / Q000502:physiology
D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D038203:alpha-Crystallin B Chain; C445081:myelin oligodendrocyte glycoprotein (35-55)