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Secretion of mediators following T lymphocyte-macrophage interaction is regulated by the major histocompatibility
Abstract:
In this study we show that T cells from mice infected with Listeria monocytogenes can interact in vitro with normal macrophages to produce a number of soluble mediators, including lymphostimulatory molecules. One of these molecules was a 15,000-dalton protein mitogenic for thymocytes. Generation of mitogenic activity was essentially completed by the first 24 hr of culture and did not require the addition of Listeria antigens. Production of mitogenic protein required contact between the lymphocytes and macrophages, because it did not occur when the two cells were separated by a cell-impermeable membrane. Optimal production of mitogenic protein occurred only when the lymphocytes and macrophages shared homologous I-A regions of the major histocompatibility complex. Once generated, the mitogenic protein did not display histocompatibility restriction and could stimulate allogeneic as well as syngeneic thymocytes. Strains of mice with the C57 background responded poorly to mitogenic protein even though those strains were capable of producing it. We conclude that an early stage in T cell immunity to Listeria involves an intimate association with macrophages regulated by the H-2 complex.
Insights
T cells and macrophages from Listeria-infected mice produce a mitogenic protein. This requires cell contact and is regulated by the major histocompatibility complex (MHC) for optimal production.
Area of Science:
- Immunology
- Cell Biology
Background:
- T cell activation and differentiation are crucial for adaptive immunity.
- Macrophage-T cell interactions play a vital role in orchestrating immune responses.
- Listeria monocytogenes infection elicits a robust T cell-mediated immune response.
Purpose of the Study:
- To investigate the soluble mediators produced by T cells interacting with macrophages in vitro.
- To characterize the properties of a specific mitogenic protein generated during this interaction.
- To elucidate the regulatory mechanisms, including cell contact and genetic factors, involved in mediator production.
Main Methods:
- Co-culture of T cells from Listeria-infected mice with normal macrophages in vitro.
- Separation of cells using a cell-impermeable membrane to assess the requirement for cell contact.
- Analysis of major histocompatibility complex (MHC) compatibility, specifically the I-A region, between interacting cells.
- Assay of thymocyte proliferation in response to the produced mediators.
- Testing the histocompatibility restriction of the generated mitogenic protein.
Main Results:
- T cells from Listeria-infected mice produced soluble mediators, including a 15,000-dalton protein mitogenic for thymocytes, upon in vitro interaction with macrophages.
- Production of this mitogenic protein was largely complete within 24 hours and did not require Listeria antigens.
- Cell contact between lymphocytes and macrophages was essential for mediator production.
- Optimal production was observed when lymphocytes and macrophages shared homologous I-A regions of the MHC.
- The produced mitogenic protein stimulated both allogeneic and syngeneic thymocytes, indicating no histocompatibility restriction after generation.
- C57 background mouse strains showed poor response to the mitogenic protein despite their ability to produce it.
Conclusions:
- An early stage of T cell immunity to Listeria involves close association with macrophages.
- This interaction is regulated by the H-2 complex (MHC).
- The study identifies a novel MHC-regulated, contact-dependent production of a thymocyte-stimulating factor by interacting T cells and macrophages.