Preferential usage of T cell receptor (TCR) V beta by allogeneic T cells recognizing myeloid leukemia cells: implications for separating graft-versus-leukemia effect from graft-versus-host disease.
New understanding of the alloresponse following bone marrow transplantation supports the possibility that the graft-versus-host disease (GVHD) response can be separated from a favorable graft-versus-leukemia (GVL) effect. We used chronic myeloid leukemia (CML) cells to generate 122 recipient-reactive T cell clones from a closely HLA-matched sibling responder. Clones were tested for their proliferative response to stimulator CML cells or PHA-transformed (non-leukemic) lymphoblasts. Of 78 clones tested, 32 recognized both leukemia cells and PHA blasts, 19 only CML and four only PHA blasts. The remainder were non-specific responders. This functional specificity corresponded to distinct patterns of T cell receptor (TCR) V beta usage: clones recognizing CML cells preferentially used V beta 5, V beta 6/7 while clones recognizing both CML and PHA blasts or only PHA blasts preferentially used V beta 3 and V beta 8. It may therefore be possible to identify in vitro-generated myeloid leukemia-restricted donor T cells by their pattern of V beta usage. TCR V beta antibodies could thus be used to select and expand leukemia-restricted donor T cells for transfusion after BMT to specifically enhance the GVL response.
Jiang
Y Z
YZ
Bone Marrow Transplantation Unit, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Mavroudis
D A
DA
Dermime
S
S
Molldrem
J
J
Hensel
N F
NF
Barrett
A J
AJ
D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D006086:Graft vs Host Disease / Q000276:immunology*; D006087:Graft vs Host Reaction / Q000276:immunology*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000276:immunology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000628:therapy*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta