ALLOREACTIVE CD4(-LYMPHOCYTES CAN EXERT CYTOTOXICITY TO CHRONIC MYELOID-LEUKEMIA CELLS PROCESSING AND PRESENTING EXOGENOUS ANTIGEN() T)

Existing evidence supports that CD4(+) T lymphocytes play a role in th e graft-versus-leukaemia (GVL) reaction after allogenic bone marrow tr ansplantation (BMT) for chronic mycloid leukaemia (CML), not only as i nitiators of the immune response but also as effectors of GVL. In BMT between HLA-identical pairs this CD4-mediated GVL would require CML ce lls to process and present antigens through MHC class II molecules. To investigate whether CML cells are capable of processing and presentin g antigens, and suitable targets for CD4(+) T-cell-mediated cytotoxici ty, we generated HLA-DR1-restricted CD4(+) cytotoxic T-cell clones tha t specifically recognized tuberculous purified protein derivative (PPD ). We have shown that CML cell and B lymphoblastoid cell line (B-LCL) cells but not PHA-blasts from patients with CML processed exogenous an tigen. PPD, and induced proliferative and cytotoxic CD4(+) T-cell resp onses. Antigen presentation was blocked by antibodies to HLA-DR but no t to MHC class I and by treatment with chloroquine and brefeldin. This indicates that CML cells use a classic MHC class II antigen processin g pathway to present PPD antigens to CD4(+) T cells. Cytotoxicity to C ML was shown by antibody blocking studies to be mediated mainly throug ht fas antigen. These findings indicate that donor CD4(+) T cells alon e are sufficient to mediate GVL effects following allogeneic BMT for C ML.