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.
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.
Welte
K
K
Laboratory of Cytokine Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Keever
C A
CA
Levick
J
J
Bonilla
M A
MA
Merluzzi
V J
VJ
Mertelsmann
R
R
Evans
R
R
O'Reilly
R J
RJ
D000328:Adult; D000371:Agglutination; D000911:Antibodies, Monoclonal; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000502:physiology; D037102:Lectins; D007938:Leukemia / Q000097:blood / Q000628:therapy*; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000628:therapy*; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D037121:Plant Lectins; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D030262:Soybean Proteins; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D010835:Phytohemagglutinins
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D037102:Lectins; D037121:Plant Lectins; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D030262:Soybean Proteins; C028824:soybean lectin; D010835:Phytohemagglutinins