Antigen presentation determines the fate of the T memory response in vivo after sublethal gamma-irradiation.
The survival of memory T cells is critical to vaccination strategies for infectious diseases and cancer, whereas their elimination may be crucial for treatment of autoimmune states. We examined the consequences of gamma-irradiation, which induces apoptosis of memory T cells in vitro, on the memory response to MHC class I alloantigen in vivo. Sublethal gamma-irradiation of primed mice eliminated accelerated rejection of skin allografts but failed to induce tolerance. Accelerated rejection was restored in irradiated mice by infusion of bone marrow cells expressing the priming alloantigen on immunostimulatory APCs (dendritic cells), whereas the memory response was not restored by infusion of bone marrow cells expressing the priming alloantigen on nonstimulatory APCs (B cells). Strikingly, irradiated mice infused with nonstimulatory bone marrow APCs exhibited long-term survival or tolerance to skin grafts expressing the priming MHC class I alloantigen. The mechanism of tolerance in this setting is explored.
Sechler
J M
JM
Division of Hematologic Products, Center for Biologics Evaluation and Research, U. S. Food and Drug Administration, Bethesda, MD 20892, USA.
Hansal
S A
SA
Morris
D I
DI
McFarland
H I
HI
Rosenberg
A S
AS
D000818:Animals; D017951:Antigen Presentation / Q000528:radiation effects*; D001402:B-Lymphocytes / Q000276:immunology / Q000528:radiation effects; D001854:Bone Marrow Cells / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D005720:Gamma Rays; D006183:H-2 Antigens / Q000235:genetics; D006801:Humans; D007108:Immune Tolerance / Q000528:radiation effects; D007074:Immunoglobulin G / Q000096:biosynthesis; D007156:Immunologic Memory / Q000528:radiation effects*; D008213:Lymphocyte Activation / Q000528:radiation effects; D008212:Lymphocyte Depletion; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D011828:Radiation Chimera / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology / Q000528:radiation effects; D016038:Skin Transplantation / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000528:radiation effects*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000528:radiation effects; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000528:radiation effects
D006183:H-2 Antigens; C024755:H-2K(K) antigen; D007074:Immunoglobulin G