We have used the murine model of spontaneous autoimmune interstitial nephritis in kdkd mice to examine the importance of abnormal immunoregulation in the expression of disease. T cells from naive congenic CBA/Ca mice suppress both histologic renal injury in the kdkd strain as well as the DTH reactivity to CBA/Ca renal tubular antigens mediated by lymphocytes from nephritic kdkd mice. These antigen-specific suppressor T cells are Lyt-2+, L3T4+, I-Jk+, genetically dominant and I-Jk restricted. Unfractionated spleen cells from young, prenephritic kdkd mice also demonstrate such suppressor function. Shortly preceding disease onset, however, net suppression is functionally bypassed by emergent contrasuppressor T cells. These regulatory cells are also Lyt-2+ and I-Jk+, and adhere both to the Vicia Villosa lectin and CBA/Ca TBM. By admixing these contrasuppressor cells with spleen cells from non-disease-prone CBA/Ca mice we were able to demonstrate the presence of DTH-reactive and nephritogenic effector cells in the latter population. Such nephritogenic effector cells could also be simply demonstrated after depletion of the suppressor cells with anti-I-Jk mAbs and complement. These findings support a role for contrasuppressor cells in the abrogation of tolerance to parenchymal self-antigens.
Contrasuppression in autoimmunity. Abnormal contrasuppression facilitates expression of nephritogenic effector T cells and interstitial nephritis in kdkd mice.
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C J Kelly, E G Neilson; Contrasuppression in autoimmunity. Abnormal contrasuppression facilitates expression of nephritogenic effector T cells and interstitial nephritis in kdkd mice.. J Exp Med 1 January 1987; 165 (1): 107–123. doi: https://doi.org/10.1084/jem.165.1.107
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