Potentiated lymphokine-activated killer cell activity generated by low-dose interleukin-2 and mismatched double-stranded RNA.
Lymphokine-activated killer (LAK) cell activity was measured in human peripheral blood mononuclear cells (PBMC) treated in vitro for 3 days with recombinant interleukin-2 (rIL-2) and mismatched double-stranded RNA (dsRNA). Lytic activity was measured utilizing K562 (NK-sensitive) and 786-0 (NK-resistant) target cells. PBMC cultured with rIL-2 (10-1000 BRMP U/ml) alone showed concentration-dependent lytic activity against the 786-0 target cells, while cells cultured in unsupplemented medium or medium supplemented with mismatched dsRNA (200 micrograms/ml) alone could not lyse the 786-0 targets. The combination of mismatched dsRNA with suboptimal concentrations of rIL-2 (10-30 U/ml) showed enhancement of both natural killer (NK) and LAK cell activities. The uptake of [3H]thymidine by treated effector cells was dependent on time and rIL-2 concentration and was not increased in the cells treated with low-dose rIL-2/mismatched dsRNA, compared to those treated with low-dose rIL-2 or mismatched dsRNA alone. Similarly, changes in the expression of CD3, CD4, CD8, CD57, CD16 and CD25 cell surface antigens were independent or rIL-2 concentration and not altered by the presence of mismatched dsRNA. These results indicate that mismatched dsRNA can potentiate rIL-2-induced LAK cell activity by increasing the functional activity per cell, rather than by increasing the number of activated cells.
Hubbell
H R
HR
Department of Neoplastic Diseases, Hahnemann University, Philadelphia, Pennsylvania 19102.
Gibson
G D
GD
Bigler
R D
RD
D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006860:Hydrogen Bonding; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000008:administration & dosage*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D012330:RNA, Double-Stranded / Q000737:chemistry / Q000494:pharmacology; D011994:Recombinant Proteins / Q000008:administration & dosage; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D012330:RNA, Double-Stranded; D011994:Recombinant Proteins