The potential of human regulatory T cells generated ex vivo as a treatment for lupus and other chronic inflammatory diseases.
Regulatory T cells prevent autoimmunity by suppressing the reactivity of potentially aggressive self-reactive T cells. Contact-dependent CD4+ CD25+ 'professional' suppressor cells and other cytokine-producing CD4+ and CD8+ T-cell subsets mediate this protective function. Evidence will be reviewed that T cells primed with transforming growth factor (TGF)-beta expand rapidly following restimulation. Certain CD4+ T cells become contact-dependent suppressor cells and other CD4+ and CD8+ cells become cytokine-producing regulatory cells. This effect is dependent upon a sufficient amount of IL-2 in the microenvironment to overcome the suppressive effects of TGF-beta. The adoptive transfer of these suppressor cells generated ex vivo can protect mice from developing chronic graft-versus-host disease with a lupus-like syndrome and alter the course of established disease. These data suggest that autologous T cells primed and expanded with TGF-beta have the potential to be used as a therapy for patients with systemic lupus erythematosus and other chronic inflammatory diseases. This novel adoptive immunotherapy also has the potential to prevent the rejection of allogeneic transplants.
Horwitz
David A
DA
The Division of Rheumatology and Immunology, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. dhorwitz@hsc.usc.edu
Gray
J Dixon
JD
Zheng
Song Guo
SG
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D017690:Cell Transplantation; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation; D015375:Receptors, Interleukin-2 / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta