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Production of interferon in mixed leukocyte cultures from two individuals
K Cantell1, S Koskimies, S Hirvonen
1National Public Health Institute, Helsinki, Finland.
Insights
Mixing leukocytes from different blood donors induced interferon (IFN) production, primarily interferon-gamma. The Human Leukocyte Antigen (HLA) DR differences, not other HLA types, influenced the amount of IFN produced.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- Interferons (IFNs) are crucial cytokines in antiviral immunity.
- Leukocyte interactions between individuals can trigger immune responses.
- The role of specific Human Leukocyte Antigen (HLA) types in spontaneous IFN production is not fully understood.
Purpose of the Study:
- To investigate spontaneous interferon production by human leukocytes.
- To determine the influence of donor leukocyte mixing on IFN production.
- To explore the correlation between HLA antigen differences and IFN-gamma/IFN-alpha/beta production.
Main Methods:
- Purified leukocytes from individual blood donors were incubated.
- Leukocytes from pairs of donors were mixed and incubated.
- Interferon (IFN) production was measured.
- HLA A, B, DQ, and DR antigen profiles of donors were analyzed.
Main Results:
- No detectable IFN was produced by leukocytes from individual donors.
- Mixing leukocytes from two donors induced IFN production, predominantly IFN-gamma, with some IFN-alpha/beta.
- IFN titers varied significantly based on donor combinations.
- No clear correlation was found between IFN production and HLA A, B, or DQ differences.
- Increased antigenic differences in HLA DR alleles correlated with higher IFN responses.
Conclusions:
- Human leukocyte interactions are a significant stimulus for spontaneous IFN production.
- HLA DR allele differences play a key role in modulating IFN-gamma and IFN-alpha/beta production between individuals.
- These findings highlight the importance of donor-specific immune interactions in cytokine responses.
Abstract:
No detectable interferon (IFN) was produced when purified leukocytes from individual blood donors were incubated without induction at 10(7) cells/ml at 37 degrees C. Mixing the leukocytes from two donors resulted in the production of IFN that was predominantly IFN-gamma but contained also some IFN-alpha/beta. The titers varied greatly depending on the combination of the two individuals. The amount of IFN produced did not bear a clear correlation to the HLA A, B, or DQ antigenic differences between the two individuals. A difference in one or two DR alleles was not always a sufficient stimulus for abundant IFN production, but more numerous antigenic DR differences tended to increase the IFN response.