HLA class II restricted T-cell reactivity to a developmentally regulated antigen shared by leukemic cells and CD34+ early progenitor cells.
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.
Mutis
T
T
Department of Immunohematology and Blood Bank, Leiden University Hospital, The Netherlands.
Schrama
E
E
van Luxemburg-Heijs
S A
SA
Falkenburg
J H
JH
Melief
C J
CJ
Goulmy
E
E
D000208:Acute Disease; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002461:Cell Line, Transformed; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006087:Graft vs Host Reaction; D006684:HLA-DR Antigens / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D004854:Herpesvirus 4, Human; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000276:immunology*
D000951:Antigens, Neoplasm; D006684:HLA-DR Antigens