Imatinib mesylate inhibits antigen-specific memory CD8 T cell responses in vivo.
Imatinib mesylate (IM) is effective at inducing complete cytogenetic remission in patients with chronic myelogenous leukemia. Because its influence on CD8 T cell responsiveness in vivo is unknown, we investigated the effects of IM by analyzing the response of OT-1 CD8 T cells to Listeria monocytogenes (LM) that express the cognate epitope OVA(257-264) (LM-OVA). In vitro, IM had no effect on Ag-specific expansion, cell division, cell cycle progression, or IFN-gamma expression in naive or memory OT-1 T cells. However, IM induced apoptosis of naive and memory OT-1 T cells at doses of >5 microM. At 15 microM IM, OT-1 T cells did not survive in in vitro cultures. The primary response of OT-1 T cells in vivo to LM-OVA infection was unaltered. In contrast, continuous IM treatment resulted in a diminished memory OT-1 response. The expression of IL-7Ralpha, a receptor required for memory cell survival, was lower (on OT-1 cells) in animals receiving IM. These results indicate that IM treatment affects the ability of the CD8 memory pool to respond to Ag and has the potential to increase susceptibility to infection.
Sinai
Parisa
P
Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Berg
Rance E
RE
Haynie
J Marshall
JM
Egorin
Merrill J
MJ
Ilaria
Robert L
RL
Forman
James
J
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D001549:Benzamides; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D000068877:Imatinib Mesylate; D007156:Immunologic Memory / Q000187:drug effects*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology; D008088:Listeriosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis / Q000276:immunology
D000942:Antigens, Bacterial; D000970:Antineoplastic Agents; D001549:Benzamides; D018984:Epitopes, T-Lymphocyte; D010879:Piperazines; D011743:Pyrimidines; D020395:Receptors, Interleukin-7; D007371:Interferon-gamma; D000068877:Imatinib Mesylate