Differential survival of transferred CD8 T cells and host reconstitution depending on TCR avidity for host-expressed alloantigen.
We transferred naive alloreactive CD8 T cells from TCR transgenic mice to irradiated recipients expressing a partial (H-2Kbm8) or a full (H-2Kb) agonist alloantigen (alloAg). The consequences were strikingly distinct, resulting in acceleration of host lymphopoiesis in the former group, but in strong graft-vs-host reaction, preventing host lymphocyte reconstitution in the latter group. This was correlated, respectively, with long-term persistence and with rapid disappearance of the transferred CD8 T cells. Analysis of transferred T cells showed that initial T cell expansion and modulation of expression of activation markers CD44 and CD62L, as well as induction of cytotoxic function, were similar in both groups. However, IL-2 production and subsequent up-regulation of CD25, early perforin-independent cytolysis, and early down-regulation of Bcl-2 expression were detected only in T cells transferred in hosts expressing full agonist alloAg. Expansion of transferred CD8 T cells was not dependent on either IL-2 or CD25 expression. This expansion could lead to either accelerated host reconstitution or to strong graft-vs-host, depending on the nature of the alloAg. Thus, the extent of Ag stimulation may be a crucial parameter in protocols of alloreactive T cell immunotherapy.
Auphan-Anezin
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N
Centre d'Immunologie de Marseille-Luminy, Centre National de la Recherche Scientifique-Institut National de la Santé et de la Recherche Médicale-Université de la Méditerranée, Campus de Luminy, Marseille, France. auphan@ciml.univ-mrs.fr
Schmitt-Verhulst
A M
AM
D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D015536:Down-Regulation / Q000276:immunology; D006087:Graft vs Host Reaction / Q000235:genetics / Q000276:immunology; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007376:Interleukin-2 / Q000502:physiology; D007519:Isoantigens / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D007700:Kinetics; D019041:L-Selectin / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D011828:Radiation Chimera / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D018960:Hyaluronan Receptors; D007376:Interleukin-2; D007519:Isoantigens; D019253:Proto-Oncogene Proteins c-bcl-2; D011948:Receptors, Antigen, T-Cell; D019041:L-Selectin