'Anergic' T cells modulate the T-cell activating capacity of antigen-presenting cells.
Nowadays there is compelling evidence for immunoregulation by T cells. Recently, we showed that so-called 'anergic' T cells are not functionally inert but can act as regulatory cells by actively suppressing other T cell responses. We now show that 'anergic' T cells mediate this suppressive effect via modulation of the T-cell activating capacity of the antigen-presenting cell (APC). Upon removal of the 'anergic' T cells, the suppressive APC phenotype persisted, indicating that 'anergic' T cells conditioned the APC to become a mediator of T cell suppression. The inhibitory signal delivered by 'anergic' T cells depended on the presence of the cognate ligand for the 'anergic' T cell, and appeared to be dominant since previously activated APC were rendered inhibitory as well. These findings imply that APC upon cross-talk with T cells can adopt distinct functional phenotypes ranging from T-cell stimulatory to T-cell suppressive. The contribution of 'anergic' T cells to the functional tuning of APC offers an explanation for the maintenance of 'anergic' T cells in the repertoire, and for their role in immunoregulation.
Taams
L S
LS
Institute of Infectious Diseases and Immunology, Department of Immunology, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.
Boot
E P
EP
van Eden
W
W
Wauben
M H
MH
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D017635:Clonal Anergy / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew
D018984:Epitopes, T-Lymphocyte