Depletion of RT6.1+ T lymphocytes induces diabetes in resistant biobreeding/Worcester (BB/W) rats.

Abstract

To investigate the role of RT6+ T cells in the pathogenesis of diabetes in BB/W rats, we treated animals from the diabetes-resistant (DR) subline with anti-RT6.1 lymphocytotoxic mAb. This depleted greater than 95% of peripheral RT6+ T cells but did not substantially reduce levels of circulating T cells or the in vitro response of spleen cells to mitogen. Treatment of 30-d-old DR BB/W rats in this way: induced insulitis and diabetes, rendered nondiabetic RT6-depleted DR rats susceptible to the adoptive transfer of diabetes by spleen cells from acutely diabetic BB/W rats, and yielded DR spleen cell populations capable of the adoptive transfer of diabetes to diabetes-prone (DP) or DR recipients. Treatment of DR rats beginning at 60 d of age failed to produce these effects. These results suggest that both susceptibility and resistance to diabetes in the BB/W rat are in part regulated by the RT6+ T cell subset and provide evidence for the importance of regulatory T lymphocytes in the pathogenesis of autoimmunity and diabetes in BB/W rats.

Susceptibility to clinically manifest cyclosporine A (CsA)-induced autoimmune disease is associated with interferon-gamma (IFN-γ)-producing CD45RC+RT6− T helper cells

“…These populations have counter-regulatory properties with respect to autoimmunity, including CsA-AI [11,[31][32][33]36,38,58,59]. In vivo manipulation of the balance between these subsets by depleting antibodies reactive with CD45RC or RT6 as well as adoptive transfer of the respective T cell subpopulations in Diabetic Prone/ BioBreeding (DP/BB) rats has shown that within the RT6 + population a protective population resides, whereas CD45RC + cells aggravate the course of disease [33,38]. Adoptive transfer studies in the model of CsA-AI have shown that adding normal splenocytes or LNC to effector cells derived from diseased rats prevents development of disease [12].…”

“…not lethal) total body x-irradiation results in the development of thyroiditis [62] and diabetes [38] in thymectomized rats and a scala of organ-specific autoimmune phenomena in mice [63]. Furthermore, depletion of RT6 + cells in diabetes-resistant (DR) BB rats leads to the development of diabetes [33]. Moreover, in the mouse CsA has been shown to result in 'forbidden V '-bearing T cells in the thymus and periphery by interference with negative selection [22,23].…”

“…CD45RC + Th cells have been shown to produce predominantly IL-2 and IFN-, whereas lymphokine production of the CD45RC -subpopulation consists mainly of IL-4 and IL-10 [31]. In previous studies balances between CD45RC + and CD45RC -Th cells or RT6 + and RT6 -Th cells were demonstrated to regulate susceptibility and development of autoimmune disease [11,[31][32][33][34][35]. Th cells capable of inducing T cell-mediated autoimmune disease are found within the CD45RC + or RT6 -subset, whereas suppressor activity is found among the CD45RC -or RT6 + Th cells [11,26,33,[36][37][38].…”

“…In previous studies balances between CD45RC + and CD45RC -Th cells or RT6 + and RT6 -Th cells were demonstrated to regulate susceptibility and development of autoimmune disease [11,[31][32][33][34][35]. Th cells capable of inducing T cell-mediated autoimmune disease are found within the CD45RC + or RT6 -subset, whereas suppressor activity is found among the CD45RC -or RT6 + Th cells [11,26,33,[36][37][38]. Altogether, in the rat the combinatory expression profiles of RT6 and CD45RC make possible the identification of four mature (Thy1.1 -) Th cell subsets with presumptive properties: CD45RC + RT6 + naive Th cells, CD45RC -RT6 -activated Th cells, CD45RC + RT6 -Th1-like memory cells, and CD45RC -RT6 + Th2-like memory cells.…”

The immunodeficient scid mouse as a model for human lymphatic filariasis.

“…Surface Ig* (B) cells were detected with an FITC goat anti-mouse IgG (heavy and light chain specific) . The percent positive cells were determined by flow cytometry as previously described (17) .…”