TY - JOUR
T1 - αB-Crystallin-reactive T cells from knockout mice are not encephalitogenic
AU - Wang, Chunhe
AU - Chou, Yuan K.
AU - Rich, Cathleen M.
AU - Link, Jason M.
AU - Afentoulis, Michael E.
AU - van Noort, Johannes M.
AU - Wawrousek, Eric F.
AU - Offner, Halina
AU - Vandenbark, Arthur A.
N1 - Funding Information:
This work was supported by a Pilot Project Award (PP0898), research grants RD3405A2, RG3400A4, RG3468A from the National Multiple Sclerosis Society, and NIH Grants NS23444, NS47661, AI43960, NS41965, NS46877, NS45445, NS49210, The Nancy Davis MS Center Without Walls, and the Biomedical Laboratory R&D Service, Department of Veterans Affairs. The authors wish to thank Sandhya Subramanian for technical assistance and Eva Niehaus for assistance in preparing this manuscript.
PY - 2006/7
Y1 - 2006/7
N2 - Alpha B-crystallin (αB) 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 αB 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 αB-knockout (αB-KO) mice in H-2b background that lack immune tolerance to αB protein, and thus are capable of developing αB-specific T cells that could be tested for encephalitogenic activity after transfer into αB-expressing wild type (WT) mice. We found that T cell lines from spleens of αB protein-immunized αB-KO mice proliferated strongly to αB protein itself, and the majority of T cells were CD4+ and capable of secreting pro-inflammatory Th1 cytokines upon restimulation. However, transfer of such αB-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, αB-specific T cells failed to augment severity of actively induced EAE in WT mice that were expressing high levels of αB message in the CNS at the time of transfer. These results suggest that αB-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 αB.
AB - Alpha B-crystallin (αB) 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 αB 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 αB-knockout (αB-KO) mice in H-2b background that lack immune tolerance to αB protein, and thus are capable of developing αB-specific T cells that could be tested for encephalitogenic activity after transfer into αB-expressing wild type (WT) mice. We found that T cell lines from spleens of αB protein-immunized αB-KO mice proliferated strongly to αB protein itself, and the majority of T cells were CD4+ and capable of secreting pro-inflammatory Th1 cytokines upon restimulation. However, transfer of such αB-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, αB-specific T cells failed to augment severity of actively induced EAE in WT mice that were expressing high levels of αB message in the CNS at the time of transfer. These results suggest that αB-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 αB.
KW - EAE/MS
KW - Knockout mice
KW - T cells
KW - Tolerance
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U2 - 10.1016/j.jneuroim.2006.04.010
DO - 10.1016/j.jneuroim.2006.04.010
M3 - Article
C2 - 16844233
AN - SCOPUS:33746040093
SN - 0165-5728
VL - 176
SP - 51
EP - 62
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -