Phenotypic and functional similarities between 5-azacytidine-treated T cells and a T cell subset in patients with active systemic lupus erythematosus.
OBJECTIVE
Antigen-specific CD4+ T cells treated with DNA methylation inhibitors become autoreactive, suggesting a novel mechanism for autoimmunity. To test whether this mechanism might be involved in systemic lupus erythematosus (SLE), phenotypic markers for the autoreactive cells were sought.


METHODS
Cloned normal T cells were treated with the DNA methylation inhibitor 5-azacytidine (5-azaC) and studied for altered gene expression. T cells from patients with active SLE were then studied for a similar change in gene expression, and cells expressing the marker were tested for autoreactivity.


RESULTS
5-azaC-treated normal T cells had increased CD11a (leukocyte function-associated antigen 1 alpha) expression relative to other membrane molecules. A T cell subset with similar CD11a expression was found in patients with active SLE. This subset contained cells that spontaneously lysed autologous macrophages, with a specificity similar to that of 5-azaC-treated cells.
Richardson
B C
BC
Department of Internal Medicine, University of Michigan, Ann Arbor.
Strahler
J R
JR
Pivirotto
T S
TS
Quddus
J
J
Bayliss
G E
GE
Gross
L A
LA
O'Rourke
K S
KS
Powers
D
D
Hanash
S M
SM
Johnson
M A
MA
D015703:Antigens, CD / Q000276:immunology; D015551:Autoimmunity / Q000502:physiology; D001374:Azacitidine / Q000494:pharmacology*; D018845:CD11 Antigens; D015180:Electrophoresis, Gel, Two-Dimensional; D005434:Flow Cytometry; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008213:Lymphocyte Activation / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D015703:Antigens, CD; D018845:CD11 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D001374:Azacitidine