GENERATION OF CD4(-LYMPHOCYTE CLONES FROM A PATIENT WITH SEVERE GRAFT-VERSUS-HOST DISEASE AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION - IMPLICATIONS FOR GRAFT-VERSUS-LEUKEMIA REACTIVITY() CYTOTOXIC T)

HLA-identical bone marrow transplantation (BMT) is associated with bot h graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) rea ctivity. Different T-cell subsets from the bone marrow (BM) graft may be responsible for GVHD and GVL reactivity after BMT. In the etiology of GVHD, not only CD8(+) but also CD4(+) donor T lymphocytes may play an important role. Here we report a patient with chronic myeloid leuke mia (CML) who was transplanted With the BM from his HLA-genotypically identical sister. After BMT there was complete engraftment, but the pa tient died because of acute GVHD grade Ill-IV in complete remission. C ytotoxic T-lymphocyte (CTL) lines were generated after BMT using the i rradiated leukemic cells from the patient as stimulator cells and the donor-originated peripheral blood mononuclear cells, procured from the patient after BMT, as responder cells. The generated CTL lines showed specific lysis of the recipient lymphocytes and leukemic cells in a C r-51 release assay. Two types of CTL clones could be established from these CTL lines, both phenotypically CD4(+). Clone type I showed male- specific HLA-DQ5-restricted lysis of the recipient lymphocytes, but no t of the circulating relatively mature leukemic cells from the patient . This may be explained by the low HLA-DQB expression of the more matu re CML cells. Clone type II showed HLA-DR2-restricted minor histocompa tibility antigen-specific lysis of the recipient lymphocytes and leuke mic cells. Both types of CTL clones showed antigen-specific cell-media ted growth inhibition of the recipient clonogenic leukemic precursor c ells. These CD4(+) CTL clones produced several activating cytokines in cluding tumor necrosis factor alpha, interferon gamma, granulocyte-mac rophage colony-stimulating factor (GM-CSF), and macrophage CSF. Our re sults illustrate that these CD4(+) CTL clones may have induced GVHD di rectly by cytolysis and indirectly by activating cytokines. Because bo th types of CTL clones recognized the recipient leukemic progenitor ce lls, they may also contribute to GVL reactivity after BMT. (C) 1995 by The American Society of Hematology.