Suppression mediated by anergic CD4+ T cells requires stimulation by MHC-peptide complexes and can be induced in the presence of costimulation.
BACKGROUND
In this study, we have investigated the mechanisms involved in both the induction of suppressive anergy, the stability of the anergy induced, and the possible mechanisms by which the response of immunocompetent CD4+ T cells are suppressed.


METHODS
We used immobilized anti-CD3 monoclonal antibody (mAb) to induce anergy in T helper (Th) 1 and Th0 cells reactive with MHC class II molecule H2 I-Ab.


RESULTS
We observed that suppressive anergy was induced independently of costimulation in Th0 but not Th1 cells. Although the anergic and suppressive states of Th0 cells were stable in the presence of exogenous interleukin-2, this was not the case for Th1 cells. No evidence for linked epitope suppression was observed for any of the I-Ab reactive cells investigated. Neither anergy nor suppression was observed in Th0 cells upon restimulation with anti-CD3 in the presence of syngeneic antigen-presenting cells (APCs). However, anergy but not suppression was observed in co-cultures restimulated with anti-T-cell antigen receptor (TCR) mAbs/syngeneic APCs and suppression could be restored by the addition of I-Ab+ APCs.


CONCLUSIONS
Overall, these data suggested that the MHC-peptide complex recognized by the Th0 cells was required for suppression of the response of immunocompetent cells. We propose that suppression is mediated either by down-modulation of the MHC-peptide complex recognized by the anergic T cells or that a molecule specific to the MHC-peptide/TCR interaction facilitates negative regulation by APC:T or T:T interactions.
Witzke
O
O
Nuffield Department of Surgery, John Radcliffe Hospital, Headington, University of Oxford, Oxford OX3 9DU, United Kingdom.
Wheeler
P R
PR
Barbara
J A
JA
Gaspar
M C
MC
Morris And
P J
PJ
Wood
K J
KJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects; D017635:Clonal Anergy / Q000187:drug effects / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D007108:Immune Tolerance / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology; D008285:Major Histocompatibility Complex / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010455:Peptides / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D018417:Th1 Cells / Q000187:drug effects / Q000502:physiology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D010455:Peptides; D011948:Receptors, Antigen, T-Cell