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Autoreactivity accelerates the development of autoimmunity and lymphoproliferation in MRL/Mp-lpr/lpr mice

Journal Article


Abstract


  • Lymph node T cells from autoimmune MRL/Mp-lpr/lpr mice, but not from congeneic MRL/Mp-+/+ mice, spontaneously proliferate and produce IL 2 when cultured in vitro for 5 to 7 days. This autologous activation depends critically on the length of in vitro culture and the initial culture density, indicating that cell to cell interaction may be essential. Phenotypic characterization of cultured cells suggest that both L3T4+ and Lyt-2+ T cells proliferate. However, only L3T4+ T cells produce IL 2. Mixing experiments reveal that the inability of freshly isolated lymph node cells from MRL/Mp-lpr/lpr mice to proliferate is not due to the presence of suppressor cells. Supernatant from 7-day cultures failed to induce freshly isolated cells to proliferate. Thus, the failure of the freshly isolated cells to spontaneously proliferate and secrete IL 2 is not due to the inability of the cells to produce soluble mediators. Similar to the inactivation of normal T lymphocytes, in vitro addition of monoclonal anti-L3T4 or anti-IL 2 receptor antibody significantly inhibits the activation of these cultured lymphocytes. Spontaneous proliferation and IL 2 production can be blocked by the addition of monoclonal anti-I-A(k) but not by monoclonal anti-I-A(d). Spontaneous proliferation and IL 2 production can be detected in young (4-wk-old) MRL/Mp-lpr/lpr mice at a time when their lymphocyte composition and physiology appear to be normal. More interestingly, spontaneous proliferation and IL 2 production cannot be detected in C57BL/6J mice bearing the lpr/lpr gene. These experiments support the notion that aberrant syngeneic autoreactivity may act as an accelerating factor in the pathogenesis of lymphoproliferation and autoimmunity in MRL/Mp-lpr/lpr mice.

Publication Date


  • 1987

Citation


  • Weston, K. M., Yeh, E. T. H., & Sy, M. S. (1987). Autoreactivity accelerates the development of autoimmunity and lymphoproliferation in MRL/Mp-lpr/lpr mice. Journal of Immunology, 139(3), 734-742.

Scopus Eid


  • 2-s2.0-0023239265

Web Of Science Accession Number


Start Page


  • 734

End Page


  • 742

Volume


  • 139

Issue


  • 3

Abstract


  • Lymph node T cells from autoimmune MRL/Mp-lpr/lpr mice, but not from congeneic MRL/Mp-+/+ mice, spontaneously proliferate and produce IL 2 when cultured in vitro for 5 to 7 days. This autologous activation depends critically on the length of in vitro culture and the initial culture density, indicating that cell to cell interaction may be essential. Phenotypic characterization of cultured cells suggest that both L3T4+ and Lyt-2+ T cells proliferate. However, only L3T4+ T cells produce IL 2. Mixing experiments reveal that the inability of freshly isolated lymph node cells from MRL/Mp-lpr/lpr mice to proliferate is not due to the presence of suppressor cells. Supernatant from 7-day cultures failed to induce freshly isolated cells to proliferate. Thus, the failure of the freshly isolated cells to spontaneously proliferate and secrete IL 2 is not due to the inability of the cells to produce soluble mediators. Similar to the inactivation of normal T lymphocytes, in vitro addition of monoclonal anti-L3T4 or anti-IL 2 receptor antibody significantly inhibits the activation of these cultured lymphocytes. Spontaneous proliferation and IL 2 production can be blocked by the addition of monoclonal anti-I-A(k) but not by monoclonal anti-I-A(d). Spontaneous proliferation and IL 2 production can be detected in young (4-wk-old) MRL/Mp-lpr/lpr mice at a time when their lymphocyte composition and physiology appear to be normal. More interestingly, spontaneous proliferation and IL 2 production cannot be detected in C57BL/6J mice bearing the lpr/lpr gene. These experiments support the notion that aberrant syngeneic autoreactivity may act as an accelerating factor in the pathogenesis of lymphoproliferation and autoimmunity in MRL/Mp-lpr/lpr mice.

Publication Date


  • 1987

Citation


  • Weston, K. M., Yeh, E. T. H., & Sy, M. S. (1987). Autoreactivity accelerates the development of autoimmunity and lymphoproliferation in MRL/Mp-lpr/lpr mice. Journal of Immunology, 139(3), 734-742.

Scopus Eid


  • 2-s2.0-0023239265

Web Of Science Accession Number


Start Page


  • 734

End Page


  • 742

Volume


  • 139

Issue


  • 3