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Pre-Clinical Studies

Alloantigen recognition is critical for CD8 T cell-mediated graft anti-tumor activity against murine BCL1 lymphoma after myeloablative bone marrow transplantation

Bone Marrow Transplantation volume 40, pages 487–497 (2007)Cite this article

Abstract

The goal of the current study was to determine whether whole bone marrow cells or splenic CD8+ T cells from C57BL/6 (H-2b) donor mice, which are tolerant to BALB/c (H-2d) alloantigens, are capable of mediating graft anti-tumor activity against a BALB/c B-cell lymphoma after injection into irradiated BALB/c hosts. The experimental results show that high doses of splenic CD8+ T cells mixed with T cell-depleted bone marrow cells from C57BL/6 non-tolerant (normal) donors eliminate the BCL1 B-cell lymphoma cells and induce lethal graft-versus-host disease (GVHD). CD8+ T cells from tolerant donors simultaneously lose both their ability to induce GVHD and their anti-tumor activity. Whole bone marrow cell transplants from normal donors eliminated BCL1 tumor cells without inducing GVHD, and bone marrow cells from tolerant donors failed to eliminate the tumor cells. The infused BCL1 tumor cells expressed an immunogenic tumor-specific idiotype antigen disparate from host alloantigens, indicating that recognition of the tumor-specific antigen alone was insufficient to elicit graft anti-tumor activity from unimmunized allotolerant donor splenic CD8+ T cells or whole bone marrow cells. We conclude that CD8+ T cells from unimmunized normal donor mice require alloantigen recognition to mediate their anti-tumor activity following allogeneic BMT.

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Acknowledgements

We acknowledge Jeanette Baker for her scientific guidance in establishing the protocol for CFSE MLR assays, Tim Knaak for assistance in cell sorting, the members of Stanford Department of Comparative Medicine for excellent animal husbandry and monitoring, and Anet James of the Stanford University Department of Pathology Photography Lab for formatting of figures. This research was supported by Grants PO1 CA-49605, PO1 HL-57443, RO1 HL-58250 and RO1 AI-37683 from the National Institutes of Health. AP was supported by NRSA Ruth Kirschtein Award # ST32HLØ7952 from the National Institutes of Health.

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  1. Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA

    A Pillai, P Teo, A Mukhopadhyay, S Dejbakhsh-Jones & S Strober

  2. Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA

    T George

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  1. A Pillai
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  2. P Teo
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  6. S Strober
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Correspondence to S Strober.

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Pillai, A., Teo, P., George, T. et al. Alloantigen recognition is critical for CD8 T cell-mediated graft anti-tumor activity against murine BCL1 lymphoma after myeloablative bone marrow transplantation. Bone Marrow Transplant 40, 487–497 (2007). https://doi.org/10.1038/sj.bmt.1705759

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