Donor cell persistence and activation-induced unresponsiveness of peripheral CD8+ T cells.
We studied the impact of the duration of donor cell persistence on CD8+ T cell responsiveness after adoptive transfer of antigen-expressing lymphoid cells. Naive or immunized female mice were treated by adoptive transfer of spleen cells from mice ubiquitously expressing a lymphocytic choriomeningitis virus-derived cytotoxic T lymphocyte (CTL) epitope (gp33-41) either alone or in combination with the male H-Y antigen providing additional antigenic CTL and T helper cell determinants. Low doses of male spleen cells (or sorted B cells) primed CTL, while high doses of the same cells rendered them unresponsive. CTL unresponsiveness induced by high numbers of male spleen cells was dependent upon prolonged persistence of antigen-expressing donor cells. Unresponsive CTL reverted to a state of activation when the duration of donor cell chimerism was limited. Memory CTL could be rendered unresponsive if antigen-expressing donor cells were allowed to persist. These results suggest that, irrespective of the type of antigen-presenting cell and the functional state of the responding T cell, activation and unresponsiveness can represent two different outcomes critically determined by quantitative and kinetic differences of antigen persistence.
Ehl
S
S
Institute of Experimental Immunology, Department of Pathology, University of Zürich, Switzerland. rolf.zinkernagel@pty.usz.ch
Barchet
W
W
Oehen
S
S
Aichele
P
P
Hombach
J
J
Hengartner
H
H
Zinkernagel
R M
RM
D019264:Adoptive Transfer; D000818:Animals; D000956:Antigens, Viral; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002678:Chimera / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D006182:H-Y Antigen / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance; D007156:Immunologic Memory; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014764:Viral Proteins
D000956:Antigens, Viral; D006023:Glycoproteins; D006182:H-Y Antigen; D010446:Peptide Fragments; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus