Activated CD4+CD25+ T cells selectively kill B lymphocytes.
The suppressive capacity of naturally occurring mouse CD4+CD25+ T cells on T-cell activation has been well documented. The present study is focused on the interaction of CD4+CD25+ T cells and B cells. By coculturing preactivated CD4+CD25+ T cells with B cells in the presence of polyclonal B-cell activators, we found that B-cell proliferation was significantly suppressed. The suppression of B-cell proliferation was due to increased cell death caused by the CD4+CD25+ T cells in a cell-contact-dependent manner. The induction of B-cell death is not mediated by Fas-Fas ligand pathway, but surprisingly, depends on the up-regulation of perforin and granzymes in the CD4+CD25+ T cells. Furthermore, activated CD4+CD25+ T cells preferentially killed antigen-presenting but not bystander B cells. Our results demonstrate that CD4+CD25+ T cells can act directly on B cells and suggest that the prevention of autoimmunity by CD4+CD25+ T cells can be explained, at least in part, by the direct regulation of B-cell function.
Zhao
Dong-Mei
DM
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg 10, Rm 11N315, Bethesda, MD 20892, USA.
Thornton
Angela M
AM
DiPaolo
Richard J
RJ
Shevach
Ethan M
EM
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018929:Cell Culture Techniques; D016923:Cell Death; D002455:Cell Division; D018920:Coculture Techniques; D005260:Female; D005434:Flow Cytometry; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000097:blood*
D015375:Receptors, Interleukin-2