Hematopoietic stem cell recipients do not develop post-transplantation immune tolerance to antigens present on minimal residual disease.

Hematopoietic stem cell recipients do not develop post-transplantation immune tolerance to antigens present on minimal residual disease. Research Abstract Details 

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Hematopoietic stem cell recipients do not develop post-transplantation immune tolerance to antigens present on minimal residual disease. Abstract Text:

Amanda Martinelli Natzke,Joanne L Shaw,Morgan R McKeller,Kris Lambert Emo,Craig A Mullen,

The immune environment present after allogeneic hematopoietic stem cell transplantation (HSCT) contributes to the control of leukemia. Our laboratory has demonstrated in a murine model that vaccination of recipients after transplantation with recipient tumor vaccines does not exacerbate graft-versus-host disease but does induce meaningful graft-versus-tumor effects. We previously demonstrated that part of the reason for the lack of graft-versus-host disease from post-transplantation vaccination is due to gradual acquisition of tolerance or unresponsiveness to recipient immunodominant minor histocompatibility antigens that are ubiquitously expressed in the recipient. However, our prior studies have not critically addressed the question of whether a similar process of acquisition of unresponsiveness to or tolerance of antigens present on minimal residual disease also occurs. The present study tested the hypothesis that unresponsiveness to antigens present on minimal residual disease present at the time of HSCT would also occur. The answer to this question would have a significant effect on the potential efficacy of post-transplantation tumor vaccines. In a murine model of major histocompatibility complex matched, minor histocompatibility antigen mismatched HSCT (C3.SW female donors and C57BL/6 female recipients), we tested whether transplant recipients would acquire unresponsiveness to antigens present on small numbers of residual leukemia/lymphoma cells. We employed a male C57BL/6 lymphoid malignancy with an immunoglobulin/c-myc oncogene in these studies using as a model of tumor-restricted antigen the well-characterized male (HY) antigen system present only on the tumor but not present as ubiquitous minor antigens in the recipient. After HSCT, recipients did not mount immune responses to the ubiquitously distributed immunodominant recipient strain H7 minor histocompatibility antigen, but did retain the capacity to mount significant T cell responses to HY antigens present on small numbers of HY+ tumor cells present at transplantation. Additional studies using small numbers of nonmalignant recipient male B cells or dendritic cells as models of minimal residual disease also demonstrated that the transplant recipients retained their capacity to mount anti-HY T cell responses. After HSCT, recipients may retain the capacity to mount effective T cell responses to antigens present on minimal residual disease and still acquire relative tolerance to ubiquitously distributed immunodominant minor antigens that are related to graft-versus-host disease.

Hematopoietic stem cell recipients do not develop post-transplantation immune tolerance to antigens present on minimal residual disease. Publishing Authors By Initials

AM Natzke,JL Shaw,MR McKeller,KL Emo,CA Mullen,

For similar investigative techniques: epidemiologic methods: statistics as topic: survival analysis research abstracts see: investigative techniques: epidemiologic methods: statistics as topic: survival analysis research

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Hematopoietic stem cell recipients do not develop post-transplantation immune tolerance to antigens present on minimal residual disease. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Biology of blood and marrow transplantation : jour

VOLUME: 13

Page Numbers: 34-45

Journal Abbreviation: Biol. Blood Marrow Transplant.

ISSN: 1083-8791

DAY: 3

MONTH: Jan

YEAR: 2007

Hematopoietic stem cell recipients do not develop post-transplantation immune tolerance to antigens present on minimal residual disease. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9600628

Hematopoietic stem cell recipients do not develop post-transplantation immune tolerance to antigens present on minimal residual disease. Keywords Mesh Terms:

KEYWORDS: Survival Analysis

MESH TERMS: immunology

Chemical & Substance for Abstract: Hematopoietic stem cell recipients do not develop post-transplantation immune tolerance to antigens present on minimal residual disease. Information

Substance Name: H-Y Antigen

Registry Number: 0

Grant and Affiliation Information for Hematopoietic stem cell recipients do not develop post-transplantation immune tolerance to antigens present on minimal residual disease.

AFFILIATION: Department of Pediatrics, University of Rochester Medical Center, Rochester, New York 14642, USA.

Country: United States

AGENCY: United States NCI

GRANT: 1R01CA10628-01

ACRONYM: CA

MEDLINETA: Biol Blood Marrow Transplant

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