In Vitro Methotrexate as a Practical Approach to Selective Allodepletion

Atul Sathe; Sterling B Ortega; Dorothy I Mundy; Robert H Collins; Nitin J Karandikar

doi:10.1016/j.bbmt.2007.01.081

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In Vitro Methotrexate as a Practical Approach to Selective Allodepletion

Journal article

Open access

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In Vitro Methotrexate as a Practical Approach to Selective Allodepletion

Atul Sathe, Sterling B Ortega, Dorothy I Mundy, Robert H Collins and Nitin J Karandikar

Biology of blood and marrow transplantation, Vol.13(6), pp.644-654

2007

DOI: 10.1016/j.bbmt.2007.01.081

PMID: 17531774

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Abstract

Graft-versus-host disease (GVHD) is a major cause of transplant-related morbidity and mortality in recipients of allogeneic hematopoietic stem cell transplantation. As GVHD is mediated predominantly by alloreactive donor T cells, selective allodepletion from the graft may alleviate GVHD, whereas potentially maintaining other advantages conferred by donor T cells, such as graft survival, antiviral immunity, and graft-versus-leukemia effect. In this study, we evaluated the ability of methotrexate, a clinically approved antimetabolite drug, to deplete alloreactive T cells in HLA-mismatched mixed lymphocyte reactions (MLR). We observed that methotrexate could inhibit the proliferation of alloreactive T cells in primary in vitro MLR. On reexposure of methotrexate-treated cells to the same allostimulus, a significant reduction in the alloreactive immune response was observed, whereas responses to third-party allostimuli and viral antigens were preserved. Thus, our results provide preclinical evidence that in vitro methotrexate treatment results in specific allodepletion and may be used as an effective agent for preventing GVHD.

Allodepletion

GVHD

Details

Title: Subtitle: In Vitro Methotrexate as a Practical Approach to Selective Allodepletion
Creators: Atul Sathe - Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, Texas
Sterling B Ortega - Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, Texas
Dorothy I Mundy - Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas
Robert H Collins - Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas
Nitin J Karandikar - Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, Texas
Resource Type: Journal article
Publication Details: Biology of blood and marrow transplantation, Vol.13(6), pp.644-654
Publisher: Elsevier Inc
DOI: 10.1016/j.bbmt.2007.01.081
PMID: 17531774
ISSN: 1083-8791
eISSN: 1523-6536
Language: English
Date published: 2007
Academic Unit: Pathology
Record Identifier: 9984047611402771

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