Defective interleukin 2 production in patients after bone marrow transplantation and in vitro restoration of defective T lymphocyte proliferation by highly purified interleukin 2

Using OKT3 monoclonal antibody as a mitogen, we have studied interleukin 2 (IL2) production and proliferation in peripheral blood mononuclear cells (PBMC) of 23 patients receiving bone marrow transplants. Twenty patients were recipients of allogeneic bone marrow for treatment of hematologic malignancies, aplastic anemias (AA), or severe combined immunodeficiencies (SCID). Three patients with Hodgkin's disease or neuroblastoma received autologous bone marrow. Endogenous IL2 production was not detectable (less than 0.2 U/mL) in PBMC of 18 patients and was very low in PBMC from five patients (0.5 to 1.5 U/mL), as compared to normal controls (median 3.5 U/mL) or pretransplant patients (median 1.5 U/mL). The low IL2 production was associated with defective OKT3-induced proliferation of PBMC in 19 of 23 patients studied. In the first 6 months after BMT, 14 of 15 patients (93%) showed defective proliferation of PBMC as compared to five of eight patients (63%) tested between 7 and 18 months after BMT (P less than .1). In all but three patients, addition of highly purified human lymphocyte IL2 (hpIL2) restored OKT3-induced proliferation of PBMC to within the normal range. This study demonstrates that PBMC in patients after BMT have a defect of IL2 production but are able to express IL2 receptors in response to OKT3 antibody and to proliferate normally upon addition of hpIL2. PBMC of all patients showed similar functional defects, whether or not they received additional therapy, including various conditioning regimens prior to BMT and immunosuppressive therapy after BMT. These observations suggest that T cell defects after BMT are most likely secondary to quantitative or qualitative defects of transplanted T lymphocytes or their precursors.