Dendritic cells pulsed with apoptotic cells activate self-reactive T-cells of lupus mice both in vitro and in vivo.
OBJECTIVE
Systemic lupus erythematosus (SLE) is characterized by the presence of autoantibodies (autoAbs) directed against the nuclear structure. Previous studies have demonstrated that dendritic cells (DCs) can process and present self-antigens (Ags) from apoptotic cells (ACs) in lupus. However, there is no direct evidence demonstrating that ACs provide self-Ags, such as histones, to stimulate autoreactive T-cells in lupus.


METHODS
AC-pulsed bone marrow-derived DCs (AC-BMDCs) were used to stimulate autoreactive T-cells in vitro and in vivo.


RESULTS
In our study, we found that AC-BMDCs could induce the proliferation of CD4+ T-cells from unprimed NZB x NZW F1 (BWF1) mice, which spontaneously develop SLE, but not CD4+ T-cells, from non-autoimmune DBA-2 x NZW F1 (DWF1) mice. In addition, AC-BMDCs could induce significant proliferative responses to certain histone peptide-specific T-cells. Furthermore, these AC-BMDCs could induce a considerable anti-DNA Ab response in vivo after adoptive transfer into DWF1 mice, suggesting that AC-BMDCs can break tolerance in normal mice and initiate an autoimmune response.


CONCLUSIONS
Our study provides a direct link between self-epitopes from ACs presented by DCs and autoreactive T-cell activation, and demonstrates that ACs are critical for the induction of autoimmunity in vivo.
Tzeng
T-C
TC
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Chung-Shan S. Road, Taipei, Taiwan, ROC.
Suen
J-L
JL
Chiang
B-L
BL
D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D017209:Apoptosis; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D004247:DNA / Q000276:immunology; D003713:Dendritic Cells / Q000637:transplantation*; D005260:Female; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000276:immunology; D007678:Kidney Glomerulus / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000628:therapy*; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D023421:Models, Animal; D010587:Phagocytosis
D001323:Autoantibodies; D016207:Cytokines; D007074:Immunoglobulin G; D004247:DNA