Impaired T and NK cell response of bone marrow and peripheral blood stem cell products to interleukin (IL)-2.
The function of steady-state and interleukin (IL)-2-co-cultured mononuclear cells differs significantly between bone marrow (BM) products, growth factor-mobilized peripheral blood stem cell (PSC) products and normal peripheral blood mononuclear cells (PBMC). The natural killer (NK) cell activity and T cell proliferative response of PSC products from non-Hodgkin's lymphoma (NHL) patients are significantly higher than that of BM products and similar to normal PBMC. However, following a five-day co-culture with IL-2 (100 IU/ml), the NK activity of PSC, PBMC, and BM products (lytic units) was increased 176-, 40-, and 14-fold, respectively, compared to that observed prior to IL-2 culture. In contrast, lymphokine activated killer (LAK) cytotoxicity prior to IL-2 culture was low in PSC and BM products and normal PBMC, but was significantly increased in PSC products and PBMC following IL-2 co-culture. The proliferative response of PSC and BM products to the T cell mitogen phytohemagglutinin (PHA) was significantly lower than that observed with normal PBMC; however, PSC had a significantly higher response than cells from BM products. Similar patterns of T cell PHA mitogenic response were observed after IL-2 co-culture. In addition, the IL-2 mitogenic responses of IL-2-co-cultured PSC and BM products were also significantly lower than that observed with PBMC co-cultured with IL-2. The IL-2 mitogenic response of PBMC was also significantly increased compared to prior to IL-2 co-culture; whereas, the IL-2 mitogenic responses from PSC and BM cells were not. In summary, co-culture with IL-2 can increase the NK and LAK cell cytotoxicity of PSC and BM products from NHL patients, but IL-2 co-culture does not improve T cell function within either BM or PSC products.
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Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-5660, USA.
Ageitos
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Heimann
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Talmadge
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D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000276:immunology; D018920:Coculture Techniques; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D007376:Interleukin-2; D010835:Phytohemagglutinins; D016179:Granulocyte Colony-Stimulating Factor