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Interleukin-2 production and response to interleukin-2 by peripheral blood
mononuclear cells from patients after bone marrow transplantation: II.
Patients receiving soybean lectin-separated and T cell-depleted bone marrow
K Welte, CA Keever, J Levick, MA Bonilla, VJ Merluzzi, R Mertelsmann, R Evans and RJ O'Reilly
Laboratory of Cytokine Biology, Memorial Sloan-Kettering Cancer Center, New
York, NY 10021.
The ability of peripheral blood mononuclear cells (PBMC) to produce and
respond to interleukin-2 (IL-2) was evaluated in 50 recipients of HLA-
identical bone marrow (BM) depleted of mature T cells by soybean
agglutination and E rosetting (SBA-E-BM). In contrast to our previous
findings in recipients of unfractionated marrow, during weeks 3 to 7
post-SBA-E-BM transplantation (BMT), PBMC from the majority of patients
spontaneously released IL-2 into the culture medium. This IL-2 was not
produced by Leu-11+ natural killer cells, which were found to be
predominant in the circulation at this time, but by T11+, T3+, Ia
antigen-bearing T cells. The IL-2 production could be enhanced by coculture
with host PBMC frozen before transplant but not by stimulation with
mitogenic amounts of OKT3 antibody, thus suggesting an in vivo activation
of donor T cells or their precursors by host tissue. Spontaneous IL-2
production was inversely proportional to the number of circulating
peripheral blood lymphocytes and ceased after 7 to 8 weeks post-SBA-E-BMT
in most of the patients. In patients whose cells had ceased to produce IL-2
spontaneously or never produced this cytokine, neither coculture with host
cells nor stimulation with OKT3 antibody thereafter induced IL-2 release
through the first year posttransplant. Proliferative responses to exogenous
IL-2 after stimulation with OKT3 antibody remained abnormal for up to 6
months post-SBA-E-BMT, unlike the responses of PBMC from recipients of
conventional BM, which responded normally by 1 month post-BMT. However, the
upregulation of IL- 2 receptor expression by exogenous IL-2 was found to be
comparable to normal controls when tested as early as 3 weeks
post-SBA-E-BMT. Therefore, the immunologic recovery of proliferative
responses to IL-2 and the appearance of cells regulating in vivo activation
of T cells appear to be more delayed in patients receiving T cell-depleted
BMT. Similar to patients receiving conventional BMT, however, the ability
to produce IL-2 after mitogenic stimulation remains depressed for up to 1
year after transplantation.
Volume 70,
Issue 5,
pp. 1595-1603,
11/01/1987
Copyright © 1987 by The American Society of Hematology
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