Suppression of disease in New Zealand Black/New Zealand White lupus-prone mice by adoptive transfer of ex vivo expanded regulatory T cells.
An increasing number of studies indicate that a subset of CD4(+) T cells with regulatory capacity (regulatory T cells; T(regs)) can function to control organ-specific autoimmune disease. To determine whether abnormalities of thymic-derived T(regs) play a role in systemic lupus erythematosus, we evaluated T(reg) prevalence and function in (New Zealand Black x New Zealand White)F(1) (B/W) lupus-prone mice. To explore the potential of T(regs) 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 T(regs) 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(+)CD62L(high) B/W T(regs) 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 T(regs) 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.
Scalapino
Kenneth J
KJ
Department of Medicine, Division of Rheumatology, University of California San Francisco, San Francisco Veterans Affairs Medical Center, CA 94121, USA.
Tang
Qizhi
Q
Bluestone
Jeffrey A
JA
Bonyhadi
Mark L
ML
Daikh
David I
DI
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology / Q000637:transplantation*