Cytotoxic and proliferative functions of T lymphocyte clones derived very shortly after allogeneic bone marrow transplantation.
In a search for mechanisms of potential graft-versus-leukaemia (GVL) activity after allogeneic bone marrow transplantation (BMT), peripheral lymphocytes from five patients (four chronic myeloid leukaemia, one acute lymphoblastic leukaemia) 24-39 days post-transplant were precultured with pretransplant host leukaemia cells and then cloned by limiting dilution with interleukin-2 (IL-2). Clones obtained were exclusively CD3+ CD56-, carried the alpha/beta form of the T cell receptor for antigen, and were mostly (88% of 138) CD4+. None of 143 clones, including CD8+ clones, convincingly lysed host pretransplant cells, although 35 (24.5%) manifested lytic potential in lectin-mediated cytotoxicity assays. Measuring the proliferative responses of 118 of these clones in the presence of exogenous IL-2 revealed that a small number of clones reacted more strongly to host leukaemia than to unrelated leukaemias or B lymphoblastoid cell lines. In the two cases tested, the donor's untransplanted lymphocytes cloned under the same conditions as post-transplant cells did not generate any clones reacting preferentially with host leukaemia cells. These results may suggest that some T cells appearing shortly after allogeneic BMT could potentially mediate anti-leukaemia activity not associated with cytolysis of target cells.
Second Department of Internal Medicine, Medical Clinic of the University of Tübingen, Germany.
W
W
Hamann
O
O
Bruserud
S
S
Patel
H
H
Schmidt
G
G
Ehninger
G
G
Pawelec
D000945:Antigens, Differentiation, T-Lymphocyte; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006086:Graft vs Host Disease / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000601:surgery; D008213:Lymphocyte Activation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000601:surgery; D013601:T-Lymphocytes / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte