Journal
CLINICAL IMMUNOLOGY
Volume 120, Issue 1, Pages 33-44Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2006.03.004
Keywords
bone marrow transplantation; recipient lymphocyte infusions; mixed chimeras; anti-tumor effects; cytotoxicity; proliferative responses; lymphocytes; indirect presentation; alloresponse; cytotoxic T lymphocyte
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Funding
- NCI NIH HHS [R01 CA79989] Funding Source: Medline
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In mixed chimeras prepared with nonmyetoablative conditioning, we previously showed that recipient leukocyte infusions (RLI) induced loss of donor chimerism and anti-tumor responses against the A20 BALB/c B cell lymphoma. We also previously showed that RLI-mediated tumor rejection involved IFN-gamma producing RLI-derived CD8(+) cells and non-RLI, recipient-derived CD4 T cells, leading to the generation of anti-tumor cytotoxic cells. However, the mechanisms of such paradoxical anti-tumor responses remained to be clarified. In the present study, we further explored the cellular mechanisms of the anti-tumor effects of RLI in fully MHC-mismatched and haploidentical strain combinations. In both cases, we show that RLI breaks the tolerance of chimeric T cells toward donor antigens, in association with the in vivo expansion of recipient splenic T, B and CD4(-)CD8(-) cells and the production of IFN-gamma. RLI leads to the development of two types of tumor-specific responses. The first is mediated by indirect presentation of donor antigens and occurs independently of tumor injection. The second is observed only in recipients of RLI and tumor and may involve responses to self antigens. Anti-tumor cytotoxicity was mediated by CD8(+) or CD4(-)CD8(-) effector cells. Thus, anti-tumor cytotoxic responses are generated following complex interactions between recipient APCs presenting donor and recipient antigens and host-type CD4(+), CD8(+) and CD4(-)CD8(-) cells. (c) 2006 Elsevier Inc. All rights reserved.
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