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

Blood. 1987 Nov;70(5):1595-603.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Agglutination
  • Antibodies, Monoclonal
  • Bone Marrow Cells
  • Bone Marrow Transplantation*
  • Cell Separation / methods
  • Cells, Cultured
  • Humans
  • In Vitro Techniques
  • Interleukin-2 / biosynthesis*
  • Interleukin-2 / physiology
  • Lectins
  • Leukemia / blood
  • Leukemia / therapy*
  • Lymphoma, Non-Hodgkin / blood
  • Lymphoma, Non-Hodgkin / therapy*
  • Middle Aged
  • Monocytes / cytology
  • Monocytes / immunology*
  • Plant Lectins*
  • Receptors, Antigen, T-Cell / analysis
  • Recombinant Proteins / pharmacology
  • Reference Values
  • Soybean Proteins*
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology

Substances

  • Antibodies, Monoclonal
  • Interleukin-2
  • Lectins
  • Plant Lectins
  • Receptors, Antigen, T-Cell
  • Recombinant Proteins
  • Soybean Proteins
  • soybean lectin