Anergic T cells actively suppress T cell responses via the antigen-presenting cell.
We here show that anergic T cells are active mediators of T cell suppression. In co-culture experiments, we found that anergic T cells, derived from established rat T cell clones and rendered anergic via T cell presentation of the specific antigen (Ag), were active inhibitors of T cell responses. Anergic T cells inhibited not only the responses of T cells with the same Ag specificity as the anergic T cells, but were also capable of efficiently inhibiting polyclonal T cell responses directed to other epitopes. This suppression required close cell-cell contact between antigen-presenting cells (APC), anergic T cells and responder T cells, and only occurred when the epitope recognized by the anergic T cell was present. The suppression was not caused by passive competition for ligands on the APC surface, IL-2 consumption, or cytolysis, and was not mediated by soluble factors derived from anergic T cells that were stimulated with their specific Ag. When responder T cells were added 24 h after co-culturing anergic cells in the presence of Ag and APC, T cell responses were still suppressed, indicating that the suppressive effect was persistently present. However, anergic T cells were not able to suppress responder T cells that had already received a full activation signal. We propose that suppression by anergic T cells is mediated via the APC, either through modulation of the T cell-activating capacity of the APC (APC/T cell interaction), or by inhibition of T cells recognizing their ligand in close proximity on the same APC (T/T cell interaction).
Taams
L S
LS
Institute of Infectious Diseases and Immunology, Department of Immunology, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.
van Rensen
A J
AJ
Poelen
M C
MC
van Els
C A
CA
Besseling
A C
AC
Wagenaar
J P
JP
van Eden
W
W
Wauben
M H
MH
D000818:Animals; D017951:Antigen Presentation; D002450:Cell Communication / Q000276:immunology*; D002999:Clone Cells; D018920:Coculture Techniques; D008213:Lymphocyte Activation; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D016176:T-Lymphocyte Subsets / Q000276:immunology*