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Published on: June 16, 2011
Bovine natural cell mediated cytotoxicity (NCMC): activation by cytokines
1Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison 53706.
Insights
Cytokines like IL-2, alpha-IFN, gamma-IFN, and IL-4 significantly boost bovine natural killer cell activity against cancer cells. However, IL-1 and beta-IFN showed no such effect on these immune cells.
Area of Science:
- Immunology
- Cell Biology
- Veterinary Science
Background:
- Bovine peripheral blood mononuclear leukocytes (PBML) possess natural cell-mediated cytotoxicity (NCMC).
- Endogenous cytotoxic activity of bovine natural effector cells (NEC) is minimal against K562 and Yac-1 target cells.
Purpose of the Study:
- To investigate the effect of various cytokines on enhancing the NCMC of bovine NEC.
- To determine the dose-dependency and kinetics of cytokine-induced NEC activation.
Main Methods:
- Incubation of bovine PBML with specific cytokines (IL-2, alpha-IFN, gamma-IFN, IL-4, IL-1, beta-IFN).
- Assessment of NCMC using a 51Cr-release assay with K562 (human) and Yac-1 (mouse) target cells.
- Evaluation of cytokine concentration and effector:target cell ratio effects.
Main Results:
- IL-2, alpha-IFN, gamma-IFN, and IL-4 significantly increased NCMC in a dose-dependent manner.
- Activation was rapid, with alpha-IFN and gamma-IFN showing effects within 6-12 hours, and IL-2 within 12-18 hours.
- IL-1 and beta-IFN did not enhance cytotoxic activity; cytokine combinations did not show synergistic effects.
Conclusions:
- Certain cytokines effectively activate bovine natural effector cells to increase NCMC.
- The activation kinetics and dose-dependency are important factors in cytokine-mediated immune responses in cattle.
- Further research into specific cytokine applications for bovine immune enhancement is warranted.
Abstract:
Incubation of bovine peripheral blood mononuclear leukocytes (PBML) with the cytokines (CK) IL-2, alpha-IFN, gamma-IFN or IL-4 resulted in significant increases in natural cell mediated cytotoxicity (NCMC) over endogenous levels, as determined in an 18 h 51Cr-release assay using the human K562 or mouse Yac-1 target cell lines. Endogenous cytotoxic activity of bovine natural effector cells (NEC) using K562 or Yac-1 target cells was minimal (killing less than 8%). After 18 h of incubation with the CK hurIL-2, alpha-bovrIFN, gamma-bovrIFN or hurIL-4, NEC had significant increases in cytotoxic activity for both K562 and Yac-1 target cells. Significant increases in cytotoxic activity were not found after incubation of NEC with IL-1 or beta-IFN. Specific killing varied with CK concentration in a dose dependent manner and was proportional to effector:target cell ratio. Activation of the bovine NEC by CK was rapid, occurring within 6-12 h of incubation with alpha-IFN or gamma-IFN and within 12-18 h of incubation with IL-2. Incubation of bovine PBML with IL-2 and alpha- or gamma-IFN or with alpha-IFN and gamma-IFN showed that these CK do not act in a synergistic manner to increase NCMC in the bovine NEC.
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