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Intra- and interspecies reactivity of human and mouse natural killer (NK) cells
Abstract:
Natural killer (NK) cells can kill certain syngeneic, allogeneic and xenogeneic tumor targets in short-term 51Cr release assays. In the present study, intra- and interspecies NK activity was analyzed. Ten mouse and five human tissue culture lines were used. In direct cytolytic assays with mouse spleen cells or human PBL effectors, intraspecies was much stronger than interspecies reactivity, as a rule. A certain interspecies activity was obtained, stronger in mouse anti-human (M alpha H) than in human anti-mouse (H alpha M) combinations. In the H alpha M system, activity was associated with the same type of PBL-derived non-B-non-T cell fraction as in the intraspecies H alpha H system. The non-B-non-T cell nature of the M alpha H killer cell has been demonstrated previously. Nonlabeled tumor cells were allowed to compete with isotope-labeled targets in intra- and interspecies cytolytic NK tests. NK-sensitive tumor lines of the same species were superior to xenogeneic competitors in both M alpha M and H alpha H tests. In the M alpha M assay, the competing ability of the same human tumors varied, depending on the genotype of the mouse effector cells. None of the human lines tested competed effectively with strain CBA effectors but some showed a certain competition with C57BL effectors. In the H alpha H assay, strong competition was seen with two of the 10 xenogeneic mouse tumors tested.
Insights
Natural killer (NK) cells exhibit stronger intraspecies activity than interspecies activity. However, some cross-species reactivity exists, with mouse anti-human combinations showing more activity than human anti-mouse, impacting tumor cell recognition.
Area of Science:
- Immunology
- Cellular and Molecular Immunology
- Cancer Immunology
Background:
- Natural killer (NK) cells are crucial immune cells capable of lysing various tumor targets.
- NK cell activity can be directed against targets within the same species (intraspecies) or across different species (interspecies).
- Understanding the specificity of NK cell responses is vital for immunotherapy and xenotransplantation research.
Purpose of the Study:
- To analyze and compare intraspecies and interspecies natural killer (NK) cell activity.
- To investigate the characteristics of NK cell-mediated cytotoxicity across different species.
- To determine the influence of tumor cell origin and effector cell genotype on NK cell recognition.
Main Methods:
- Direct cytolytic assays using mouse spleen cells and human peripheral blood lymphocytes (PBLs) as effectors against various mouse and human tumor cell lines.
- Competition assays using unlabeled tumor cells to assess the ability of xenogeneic tumor cells to inhibit NK cell-mediated lysis of labeled syngeneic targets.
- Analysis of effector cell fractions to identify the cell types responsible for interspecies NK activity.
Main Results:
- Intraspecies NK activity was consistently stronger than interspecies activity in both mouse and human systems.
- Mouse anti-human (MαH) NK activity was generally stronger than human anti-mouse (HαM) activity.
- Interspecies NK activity was mediated by non-B, non-T lymphocytes, similar to intraspecies NK cells.
- NK-sensitive tumor lines of the same species were more effective competitors than xenogeneic tumor cells.
- The competitive ability of human tumors varied against different mouse effector cell genotypes.
Conclusions:
- NK cell-mediated cytotoxicity is primarily species-specific, with a preference for intraspecies targets.
- A degree of cross-species NK cell recognition exists, particularly in mouse anti-human combinations.
- The genetic makeup of effector cells influences the recognition of xenogeneic targets by NK cells.