Hla class II restricted T-cell reactivity to a developmentally regulated antigen shared by leukemic cells and CD34+ early progenitor cells

Tuna Mutis, Ellen Schrama, Simone A P Van Luxemburg-Heijs, J. H F Falkenburg, Cornelis J M Melief, Els Goulmy

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

After allogeneic bone marrow transplantation (BMT), the beneficial graft-versus-leukemia (GVL) effect but also the life-threatening graft- versus-host disease (GVHD) are mediated by T cells of the grafted marrow. The identification of leukemia cell-reactive T cells and their ligands are, therefore, crucial for the development of new anti-leukemia strategies. Here we describe a leukemia-reactive allo-HLA class II restricted CD4+ T-cell clone, 6.2, isolated from a healthy individual after stimulation with allogeneic leukemic cells. Clone 6.2 recognizes leukemic cells from several AML patients without showing reactivity to unfractioned peripheral blood mononuclear cells, monocytes, B cells, T-cell blasts, and proximal tubulus epithelial cells. Interestingly, clone 6.2 also recognizes BM cells derived from healthy individuals and inhibits the colony formation of myeloid and erythroid cell lineages. In the BM, clone 6.2 recognizes only CD34+ early precursor cells but not CD34+, more differentiated cells. Thus, the target antigen of clone 6.2 is developmentally regulated and expressed only by leukemic cells and CD34+ early progenitor cells in the hematopoietic system. We suggest that targeting the T-cell immune response to leukemia-associated, developmentally regulated antigens of the hematopoietic system can provide a basis for the separation of GVL from GVHD, and may lead to new therapeutic approaches for residual and relapsed leukemia.

Original languageEnglish
Pages (from-to)1083-1090
Number of pages8
JournalBlood
Volume90
Issue number3
Publication statusPublished - 1 Aug 1997

Cite this

Mutis, T., Schrama, E., Van Luxemburg-Heijs, S. A. P., Falkenburg, J. H. F., Melief, C. J. M., & Goulmy, E. (1997). Hla class II restricted T-cell reactivity to a developmentally regulated antigen shared by leukemic cells and CD34+ early progenitor cells. Blood, 90(3), 1083-1090.
Mutis, Tuna ; Schrama, Ellen ; Van Luxemburg-Heijs, Simone A P ; Falkenburg, J. H F ; Melief, Cornelis J M ; Goulmy, Els. / Hla class II restricted T-cell reactivity to a developmentally regulated antigen shared by leukemic cells and CD34+ early progenitor cells. In: Blood. 1997 ; Vol. 90, No. 3. pp. 1083-1090.
@article{46a14c4f8d524b4bbd1cf4525907184e,
title = "Hla class II restricted T-cell reactivity to a developmentally regulated antigen shared by leukemic cells and CD34+ early progenitor cells",
abstract = "After allogeneic bone marrow transplantation (BMT), the beneficial graft-versus-leukemia (GVL) effect but also the life-threatening graft- versus-host disease (GVHD) are mediated by T cells of the grafted marrow. The identification of leukemia cell-reactive T cells and their ligands are, therefore, crucial for the development of new anti-leukemia strategies. Here we describe a leukemia-reactive allo-HLA class II restricted CD4+ T-cell clone, 6.2, isolated from a healthy individual after stimulation with allogeneic leukemic cells. Clone 6.2 recognizes leukemic cells from several AML patients without showing reactivity to unfractioned peripheral blood mononuclear cells, monocytes, B cells, T-cell blasts, and proximal tubulus epithelial cells. Interestingly, clone 6.2 also recognizes BM cells derived from healthy individuals and inhibits the colony formation of myeloid and erythroid cell lineages. In the BM, clone 6.2 recognizes only CD34+ early precursor cells but not CD34+, more differentiated cells. Thus, the target antigen of clone 6.2 is developmentally regulated and expressed only by leukemic cells and CD34+ early progenitor cells in the hematopoietic system. We suggest that targeting the T-cell immune response to leukemia-associated, developmentally regulated antigens of the hematopoietic system can provide a basis for the separation of GVL from GVHD, and may lead to new therapeutic approaches for residual and relapsed leukemia.",
author = "Tuna Mutis and Ellen Schrama and {Van Luxemburg-Heijs}, {Simone A P} and Falkenburg, {J. H F} and Melief, {Cornelis J M} and Els Goulmy",
year = "1997",
month = "8",
day = "1",
language = "English",
volume = "90",
pages = "1083--1090",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "3",

}

Mutis, T, Schrama, E, Van Luxemburg-Heijs, SAP, Falkenburg, JHF, Melief, CJM & Goulmy, E 1997, 'Hla class II restricted T-cell reactivity to a developmentally regulated antigen shared by leukemic cells and CD34+ early progenitor cells' Blood, vol. 90, no. 3, pp. 1083-1090.

Hla class II restricted T-cell reactivity to a developmentally regulated antigen shared by leukemic cells and CD34+ early progenitor cells. / Mutis, Tuna; Schrama, Ellen; Van Luxemburg-Heijs, Simone A P; Falkenburg, J. H F; Melief, Cornelis J M; Goulmy, Els.

In: Blood, Vol. 90, No. 3, 01.08.1997, p. 1083-1090.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Hla class II restricted T-cell reactivity to a developmentally regulated antigen shared by leukemic cells and CD34+ early progenitor cells

AU - Mutis, Tuna

AU - Schrama, Ellen

AU - Van Luxemburg-Heijs, Simone A P

AU - Falkenburg, J. H F

AU - Melief, Cornelis J M

AU - Goulmy, Els

PY - 1997/8/1

Y1 - 1997/8/1

N2 - After allogeneic bone marrow transplantation (BMT), the beneficial graft-versus-leukemia (GVL) effect but also the life-threatening graft- versus-host disease (GVHD) are mediated by T cells of the grafted marrow. The identification of leukemia cell-reactive T cells and their ligands are, therefore, crucial for the development of new anti-leukemia strategies. Here we describe a leukemia-reactive allo-HLA class II restricted CD4+ T-cell clone, 6.2, isolated from a healthy individual after stimulation with allogeneic leukemic cells. Clone 6.2 recognizes leukemic cells from several AML patients without showing reactivity to unfractioned peripheral blood mononuclear cells, monocytes, B cells, T-cell blasts, and proximal tubulus epithelial cells. Interestingly, clone 6.2 also recognizes BM cells derived from healthy individuals and inhibits the colony formation of myeloid and erythroid cell lineages. In the BM, clone 6.2 recognizes only CD34+ early precursor cells but not CD34+, more differentiated cells. Thus, the target antigen of clone 6.2 is developmentally regulated and expressed only by leukemic cells and CD34+ early progenitor cells in the hematopoietic system. We suggest that targeting the T-cell immune response to leukemia-associated, developmentally regulated antigens of the hematopoietic system can provide a basis for the separation of GVL from GVHD, and may lead to new therapeutic approaches for residual and relapsed leukemia.

AB - After allogeneic bone marrow transplantation (BMT), the beneficial graft-versus-leukemia (GVL) effect but also the life-threatening graft- versus-host disease (GVHD) are mediated by T cells of the grafted marrow. The identification of leukemia cell-reactive T cells and their ligands are, therefore, crucial for the development of new anti-leukemia strategies. Here we describe a leukemia-reactive allo-HLA class II restricted CD4+ T-cell clone, 6.2, isolated from a healthy individual after stimulation with allogeneic leukemic cells. Clone 6.2 recognizes leukemic cells from several AML patients without showing reactivity to unfractioned peripheral blood mononuclear cells, monocytes, B cells, T-cell blasts, and proximal tubulus epithelial cells. Interestingly, clone 6.2 also recognizes BM cells derived from healthy individuals and inhibits the colony formation of myeloid and erythroid cell lineages. In the BM, clone 6.2 recognizes only CD34+ early precursor cells but not CD34+, more differentiated cells. Thus, the target antigen of clone 6.2 is developmentally regulated and expressed only by leukemic cells and CD34+ early progenitor cells in the hematopoietic system. We suggest that targeting the T-cell immune response to leukemia-associated, developmentally regulated antigens of the hematopoietic system can provide a basis for the separation of GVL from GVHD, and may lead to new therapeutic approaches for residual and relapsed leukemia.

UR - http://www.scopus.com/inward/record.url?scp=0030740588&partnerID=8YFLogxK

M3 - Article

VL - 90

SP - 1083

EP - 1090

JO - Blood

JF - Blood

SN - 0006-4971

IS - 3

ER -

Mutis T, Schrama E, Van Luxemburg-Heijs SAP, Falkenburg JHF, Melief CJM, Goulmy E. Hla class II restricted T-cell reactivity to a developmentally regulated antigen shared by leukemic cells and CD34+ early progenitor cells. Blood. 1997 Aug 1;90(3):1083-1090.