Spontaneous autocytotoxicity against an unexpected H-2
d haplotype in MRL/lpr (H-2
k) autoimmune disease-prone mice |
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Authors: | Pierre Bobé Gabriel Gachelin Nicole Kiger |
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Institution: | (1) INSERM U. 277-CNRS UA 535, Institut Pasteur, 25, rue du Docteur Roux, F-75724 Paris Cedex 15, France;(2) INSERM U. 283, Hôpital Cochin, 27, rue du Faubourg Saint-Jacques, F-75674 Paris Cedex 14, France |
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Abstract: | The MRL/lpr (H-2
k) inbred strain, a model for the autoimmune disease systemic lupus erythematosus, differs from the healthy inbred strain MRL +/+ (H-2
k) by only 0.1 % of its genome. Southern blot analysis using class I and class II probes confirmed the H-2
k genotype of both strains. Among the Iak-positive peritoneal cells, cells with an unexpected expression of Iad specificities were detected in a radioimmunoassay using several monoclonal antibodies and one conventional antiserum. This was only found in aged (6- to 9-month-old) mice both in the MRL/lpr strain (32 % Iad-positive mice) and in the MRL +/+ strain (42% Iad-positive mice). Furthermore, 24% of aged MRL/lpr mice exhibited strong spontaneous cytotoxic T lymphocyte (CTL) activities against P815 (H-2
d) target cells, and 57% had a weaker but still detectable level of cytotoxicity. In contrast, such a CTL activity has never been found in the MRL +/+ strain. These results suggest that the anti-H-2d d CTL plays a role in the onset of the autoimmune process in MRL/lpr mice. |
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