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Defective interleukin 2 production in patients after bone marrow
transplantation and in vitro restoration of defective T lymphocyte
proliferation by highly purified interleukin 2
K Welte, N Ciobanu, MA Moore, S Gulati, RJ O'Reilly and R Mertelsmann
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.
Volume 64,
Issue 2,
pp. 380-385,
08/01/1984
Copyright © 1984 by The American Society of Hematology
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