Allogeneic bone marrow cells that facilitate complete chimerism and eliminate tumor cells express both CD8 and T-cell antigen receptor–αβ

Lan, Fengshuo; Zeng, Defu; Huie, Philip; Higgins, Julian P T; Strober, Samuel

doi:10.1182/blood.v97.11.3458

Cited by 20 publications

(30 citation statements)

References 33 publications

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“…Tissues were fixed in 10% formalin, embedded in paraffin blocks, and 4-to 5-mm sections were stained with hematoxylin and eosin using standard protocols. [1][2][3] Microscopic images were obtained using an Eclipse E1000M microscope (Nikon, Melville, NY, USA) with SPOT RT digital camera and acquisition software (Diagnostic Instruments, Sterling Heights, MI, USA) with final magnification (objective, Â 20/0.45 numerical aperture) provided with each figure. Image processing was performed with Photoshop CS (Abode Systems, San Jose, CA, USA) with standard adjustments of brightness, contrast and color balance to the entire image.…”

Section: Bone Marrow and Mononuclear Cell Infusionmentioning

confidence: 99%

“…Cells were washed twice with 0.05% sodium azide staining buffer and incubated on ice for 20 min with saturating concentrations of monoclonal antibody mixtures as described previously. [1][2][3] All mouse cells were incubated with CD16/32 (2.4G2, Becton-Dickinson, San Diego, CA, USA) before antibody staining to block FcRg II/III receptors. The following conjugated mAbs were used: APC anti-TCRab clone H57-597, PE anti-Ly6C (Gr-1) clone RB6-8C5, PE anti-CD11b (Mac-1a) clone M1/70, biotin-anti-CD8 clone 53-6.7, PE anti-B220 clone RA3-6B2, FITC anti-H-2K b clone AF6-88.5 (Becton-Dickinson, San Diego, CA, USA), and Streptavidin -Texas Red (Molecular Probes, Eugene, OR, USA).…”

Section: Cell Preparationmentioning

confidence: 99%

“…Nevertheless, C57BL/6 marrow CD8 þ T cells maintained potent graft anti-tumor activity against BCL 1 , a BALB/c-derived lymphoma. 2,3 However, the role of alloantigen versus tumor antigen recognition in graft anti-tumor activity of the marrow T cells is not clear, as the BCL 1 tumor expresses an immunogenic IgM-l idiotype tumor antigen. 4 BCL 1 tumor cells can be eliminated by the adoptive transfer of T cells from syngeneic hosts that have been immunized to the idiotype antigen.…”

Section: Introductionmentioning

confidence: 99%

“…1,2 In contrast to splenic CD8 þ T cells, CD8 þ T cells purified from wild-type C57BL/6 donor bone marrow mediate the killing of BCL 1 tumor cells without inducing GVHD over a wide dose range. 1,2 Tumor killing by CD8 þ T cells from the marrow was reduced or lost when perforin À/À or Fas ligand À/À (FasL À/À ) C57BL/6 mice were used as donors. 2 However, the relative contribution of alloantigen versus tumorspecific antigen recognition in the graft anti-tumor activity of donor splenic or marrow CD8 þ T cells has not been elucidated clearly in these major histocompatibility complex (MHC)-mismatched model systems using donors that are not immunized to the tumor antigens.…”

Section: Introductionmentioning

confidence: 99%

“…2 There is a narrow dose range of purified splenic CD8 þ T cells that effectively kills the BALB/c-derived BCL 1 lymphoma without inducing lethal GVHD. 1,2 In contrast to splenic CD8 þ T cells, CD8 þ T cells purified from wild-type C57BL/6 donor bone marrow mediate the killing of BCL 1 tumor cells without inducing GVHD over a wide dose range. 1,2 Tumor killing by CD8 þ T cells from the marrow was reduced or lost when perforin À/À or Fas ligand À/À (FasL À/À ) C57BL/6 mice were used as donors.…”

Section: Introductionmentioning

confidence: 99%

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

Pillai

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Section: Bone Marrow and Mononuclear Cell Infusionmentioning

confidence: 99%

Section: Cell Preparationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Pillai

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George

et al. 2007

Bone Marrow Transplant

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Hepatic parenchymal replacement in mice by transplanted allogeneic hepatocytes is facilitated by bone marrow transplantation and mediated by CD4 cells

et al. 2008

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The lack of adequate donor organs is a major limitation to the successful widespread use of liver transplantation for numerous human hepatic diseases. A desirable alternative therapeutic option is hepatocyte transplantation (HT), but this approach is similarly restricted by a shortage of donor cells and by immunological barriers. Therefore, in vivo expansion of tolerized transplanted cells is emerging as a novel and clinically relevant potential alternative cellular therapy. Toward this aim, in the present study we established a new mouse model that combines HT with prior bone marrow transplantation (BMT). Donor hepatocytes were derived from human alpha(1)-antitrypsin (hAAT) transgenic mice of the FVB strain. Serial serum enzyme-linked immunosorbent assays for hAAT protein were used to monitor hepatocyte engraftment and expansion. In control recipient mice lacking BMT, we observed long-term yet modest hepatocyte engraftment. In contrast, animals undergoing additional syngeneic BMT prior to HT showed a 3-to 5-fold increase in serum hAAT levels after 24 weeks. Moreover, complete liver repopulation was observed in hepatocyte-transplanted Balb/C mice that had been transplanted with allogeneic FVB-derived bone marrow. These findings were validated by a comparison of hAAT levels between donor and recipient mice and by hAAT-specific immunostaining. Taken T o date, orthotopic liver transplantation remains the only therapeutic option for many acute and chronic end-stage liver diseases. However, donor organs are limited and can be used to treat only one patient at a time. Thus, great efforts are underway to explore new strategies for parenchymal liver cell replacement. Hepatocyte transplantation (HT) is currently the most promising option as hepatocytes have been proven to possess tremendous in vivo expansion capability, require little pretransplant manipulation, and may permit the distribution of cells from a single donor organ to multiple recipients. However, because of technical restraints, only a limited number of hepatocytes can be transplanted at a time; moreover, donor cells may be subject to immune surveillance. This raises an urgent need to develop novel strategies to induce tolerance and to select donor cells for in vivo expansion.Recent studies in the field of HT have concentrated on animal models for liver repopulation and on the determination of intrinsic factors driving the in vivo expansion of

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Adoptive cancer immunotherapy: discovering the best targets.

Perreault

Brochu

2002

J Mol Med

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Numerous animal and clinical studies have shown that injection of T lymphocytes from a major histocompatibility complex matched donor can cure subjects with chemotherapy-resistant hematological malignancies. This graft-versus-tumor effect, which represents the most conclusive evidence that the immune system can cure cancer in humans, is mediated primarily if not exclusively by T cells specific for host minor histocompatibility antigens. Since minor histocompatibility antigens are present on all tissues and organs, injection of unselected donor T cells also causes graft vs. host disease, which drastically limits the use and benefits of this treatment. Recent studies in mice have shown that adoptive transfer of primed T cells targeted to a single major histocompatibility complex class I restricted immunodominant minor histocompatibility antigen can eradicate leukemia cells without causing any toxicity to the host. We present the promises and caveats of this and other new approaches for adoptive T cell immunotherapy of cancer.

show abstract

Allogeneic bone marrow cells that facilitate complete chimerism and eliminate tumor cells express both CD8 and T-cell antigen receptor–αβ

Cited by 20 publications

References 33 publications

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

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

Hepatic parenchymal replacement in mice by transplanted allogeneic hepatocytes is facilitated by bone marrow transplantation and mediated by CD4 cells

Adoptive cancer immunotherapy: discovering the best targets.

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