MRL/Mp CD4+,CD25- T cells show reduced sensitivity to suppression by CD4+,CD25+ regulatory T cells in vitro: a novel defect of T cell regulation in systemic lupus erythematosus.
OBJECTIVE
To investigate the hypothesis that loss of suppression mediated by peripheral CD4+,CD25+ regulatory T cells is a hallmark of systemic lupus erythematosus (SLE).


METHODS
Mice of the MRL/Mp strain were studied as a polygenic model of SLE. Following immunomagnetic selection, peripheral lymphoid CD25+ and CD25- CD4+ T cells were cultured independently or together in the presence of anti-CD3/CD28 monoclonal antibody-coated beads. Proliferation was assessed by measuring the incorporation of tritiated thymidine.


RESULTS
While MRL/Mp CD4+,CD25+ regulatory T cells showed only subtle abnormalities of regulatory function in vitro, syngeneic CD4+,CD25- T cells showed significantly reduced sensitivity to suppression, as determined by crossover experiments in which MRL/Mp CD4+,CD25- T cells were cultured with H-2-matched CBA/Ca CD4+,CD25+ regulatory T cells in the presence of a polyclonal stimulus.


CONCLUSIONS
Our findings highlight a novel defect of peripheral tolerance in SLE. Identification of this defect could open new opportunities for therapeutic intervention.
Monk
C R
CR
Imperial College London, Hammersmith Campus, London, UK.
Spachidou
M
M
Rovis
F
F
Leung
E
E
Botto
M
M
Lechler
R I
RI
Garden
O A
OA
D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D005434:Flow Cytometry; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D051379:Mice; D019463:Mice, Inbred MRL lpr / Q000235:genetics / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D017634:Self Tolerance / Q000276:immunology*; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000648:ultrastructure; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000648:ultrastructure
D015375:Receptors, Interleukin-2