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Published on: August 12, 2017
Suppression of primary allogenic response by CD8+ memory cells
T S Grinenko1, E L Pobezinskaya, L A Pobezinskii
1N. N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Moscow.
Insights
Long-lived CD8+ memory cells are generated after exposure to allogenic tumor cells. These memory cells can suppress naive cells and produce IL-10, indicating a role in regulating immune responses.
Area of Science:
- Immunology
- Cellular Immunology
- Tumor Immunology
Background:
- Allogeneic tumor cell exposure elicits immune responses involving long-lived CD8+ memory cells.
- These CD8+ memory cells exhibit rapid restimulation and cytotoxic capabilities against tumor cells upon re-exposure.
Purpose of the Study:
- To investigate the functional characteristics of allorestricted CD8+ memory cells.
- To understand the conditions required for memory cell effector function acquisition.
- To explore the immunomodulatory properties of memory cells in vitro.
Main Methods:
- Induction of immune response to allogeneic tumor cells.
- Assessment of CD8+ memory cell restimulation and cytotoxic activity.
- In vitro co-culture assays with naive splenocytes and mixed lymphocyte cultures.
- Analysis of cytokine production (IL-10, IL-2) following antigen stimulation.
Main Results:
- Allorestricted memory cells require 2 days of antigen restimulation to acquire effector function, characteristic of central memory cells.
- Memory cells demonstrate the ability to suppress the proliferation of naive splenocytes in vitro.
- Antigen stimulation in memory cell-containing mixed lymphocyte cultures leads to increased IL-10 production and suppressed IL-2 production compared to naive cells.
- Conditions for naive cell activation during a secondary immune response are suboptimal.
Conclusions:
- CD8+ memory cells generated against allogeneic tumors possess unique functional properties, including antigen-specific suppression.
- Memory cell activation involves a distinct timeframe for effector function acquisition.
- These memory cells play a role in modulating immune responses through cytokine production, notably IL-10.
- The findings suggest a complex regulatory network during secondary immune responses involving memory cell populations.
Abstract:
Immune response to allogenic tumor cells is associated with the appearance of long-living CD8+ memory cells capable of rapid restimulation and lysis of tumor cells in case of repeated injection of these cells. In order to acquire the effector function, allorestricted memory cells need antigen restimulation for 2 days, which is a specific feature of central memory cell population. These cells can suppress proliferation of naive splenocytes in vitro. In mixed lymphocyte cultures containing memory cells, antigen stimulation induces more intensive IL-10 production and deeper suppression of IL-2 production in comparison with cultures containing naive cells. The conditions for activation of naive cells during secondary immune response are not optimal.
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