T helper target cell DNA fragmentation through a CD4-positive T suppressor cell clone inducing specific unresponsiveness.
The CD4-positive bovine serum albumin (BSA)-specific Ts cell clone BVI/5 from a CBA/J mouse tolerized to low doses of BSA induces specific unresponsiveness in the T helper (Th) cell population. Tolerance induction can be measured in vitro in proliferation assays using specific Th cell clones or antigen-primed lymph node cells (LNC) and determined in vivo by the failure to produce hapten-specific antibodies. Using the BSA-specific Th cell clone 83/1 as a target one observes in addition 51Cr-release in a 16-hr long-term assay but finds no effect in a typical 6-hr T cell cytotoxicity test. BVI/5 Ts cells do not produce interleukin-2 but otherwise express a Th1 profile. The suppression of proliferation of 83/1 Th cells is partly due to interferon-gamma (IFN-gamma). But lysis of 83/1 Th cells as well as suppression of BSA-specific LNC proliferation needs direct cell contact between BVI/5 Ts cells and their targets. Cell lysis and suppression of LNC cannot be simulated by IFN-gamma, by the combination of IFN-gamma and TNF, or by BVI/5 supernatants. Thus mediators cannot account for specific suppression by BVI/5 Ts cells in polyclonal in vitro responses from LNC and are probably not responsible for the induction of in vivo unresponsiveness. Instead the data show that BVI/5 Ts cells induce apoptosis-like DNA fragmentation in cloned BSA-specific 83/1 Th cells and in LNC from BSA-primed mice. Apoptosis can also be visualized as chromatin condensation in the LNC population. Macrophages have been excluded as targets. It can further be demonstrated that BVI/5 Ts cells express perforin and granzyme A on activation. Thus they are equipped with the effector molecules for target cell destruction. We consider BVI/5 Ts cells to be representative of a regulatory T cell inducing specific unresponsiveness in peripheral lymphoid organs.
Becker
C
C
Institut für Immunologie, Universität Münster, Germany.
Konur
A
A
Rademaekers
A
A
Kodelja
V
V
Partenheimer
A
A
Pauels
H G
HG
Kölsch
E
E
D000818:Animals; D000941:Antigens; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004249:DNA Damage / Q000276:immunology*; D015870:Gene Expression; D053804:Granzymes; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000235:genetics; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008808:Mice, Inbred CBA; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000235:genetics; D012710:Serum Albumin, Bovine / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000941:Antigens; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D012710:Serum Albumin, Bovine; D053804:Granzymes; D012697:Serine Endopeptidases