TY - JOUR
T1 - Suppression of disease in New Zealand Black/New Zealand White lupus-prone mice by adoptive transfer of ex vivo expanded regulatory T cells
AU - Scalapino, Kenneth J.
AU - Tang, Qizhi
AU - Bluestone, Jeffrey A.
AU - Bonyhadi, Mark L.
AU - Daikh, David I.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2006/8/1
Y1 - 2006/8/1
N2 - An increasing number of studies indicate that a subset of CD4+ T cells with regulatory capacity (regulatory T cells; Tregs) can function to control organ-specific autoimmune disease. To determine whether abnormalities of thymic-derived Tregs play a role in systemic lupus erythematosus, we evaluated Treg prevalence and function in (New Zealand Black × New Zealand White)F1 (BAV) lupus-prone mice. To explore the potential of Tregs to suppress disease, we evaluated the effect of adoptive transfer of purified, ex vivo expanded thymic-derived T regs on the progression of renal disease. We found that although the prevalence of Tregs is reduced in regional lymph nodes and spleen of prediseased B/W mice compared with age-matched non-autoimmune mice, these cells increase in number in older diseased mice. In addition, the ability of these cells to proliferate in vitro was comparable to those purified from non-autoimmune control animals. Purified CD4+CD25 +CD62Lhigh B/W Tregs were expanded ex vivo 80-fold, resulting in cells with a stable suppressor phenotype. Adoptive transfer of these exogenously expanded cells reduced the rate at which mice developed renal disease; a second transfer after treated animals had developed proteinuria further slowed the progression of renal disease and significantly improved survival. These studies indicate that thymic-derived Tregs may have a significant role in the control of autoimmunity in lupus-prone B/W mice, and augmentation of these cells may constitute a novel therapeutic approach for systemic lupus erythematosus.
AB - An increasing number of studies indicate that a subset of CD4+ T cells with regulatory capacity (regulatory T cells; Tregs) can function to control organ-specific autoimmune disease. To determine whether abnormalities of thymic-derived Tregs play a role in systemic lupus erythematosus, we evaluated Treg prevalence and function in (New Zealand Black × New Zealand White)F1 (BAV) lupus-prone mice. To explore the potential of Tregs to suppress disease, we evaluated the effect of adoptive transfer of purified, ex vivo expanded thymic-derived T regs on the progression of renal disease. We found that although the prevalence of Tregs is reduced in regional lymph nodes and spleen of prediseased B/W mice compared with age-matched non-autoimmune mice, these cells increase in number in older diseased mice. In addition, the ability of these cells to proliferate in vitro was comparable to those purified from non-autoimmune control animals. Purified CD4+CD25 +CD62Lhigh B/W Tregs were expanded ex vivo 80-fold, resulting in cells with a stable suppressor phenotype. Adoptive transfer of these exogenously expanded cells reduced the rate at which mice developed renal disease; a second transfer after treated animals had developed proteinuria further slowed the progression of renal disease and significantly improved survival. These studies indicate that thymic-derived Tregs may have a significant role in the control of autoimmunity in lupus-prone B/W mice, and augmentation of these cells may constitute a novel therapeutic approach for systemic lupus erythematosus.
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U2 - 10.4049/jimmunol.177.3.1451
DO - 10.4049/jimmunol.177.3.1451
M3 - Article
C2 - 16849451
AN - SCOPUS:33746214867
SN - 0022-1767
VL - 177
SP - 1451
EP - 1459
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -