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Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity
Published on: June 7, 2017
Characterization of the CD8+CD45R+(2H4+) suppressor effector cell
C Morimoto1, T Takeuchi, S F Schlossman
1Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA.
Insights
CD8 cells with CD45R antigen show suppressor activity after autologous mixed lymphocyte reaction (AMLR) activation. This suppressor function relies on CD45R and the CD3-T cell receptor (TCR) complex.
Area of Science:
- Immunology
- Cell Biology
Background:
- CD8 cells play crucial roles in immune regulation.
- Autologous mixed lymphocyte reaction (AMLR) is a model for studying T cell activation and regulation.
- The specific subsets and molecular mechanisms underlying CD8+ cell-mediated suppression after AMLR are not fully understood.
Purpose of the Study:
- To elucidate the molecular basis of immunoregulatory function in CD8 cells following AMLR activation.
- To identify the specific CD8+ cell subpopulations responsible for suppressor activity post-AMLR.
- To investigate the role of CD45R and the CD3-T cell receptor (TCR) complex in CD8+ cell-mediated suppression.
Main Methods:
- Activation of CD8+ cells via autologous mixed lymphocyte reaction (AMLR).
- Subsetting of CD8+ cells based on CD45R expression (CD8+CD45R+ and CD8+CD45R-).
- Assessment of suppressor and cytotoxic activities of cell subsets.
- Functional blockade of CD45R and CD3 using specific antibodies.
Main Results:
- The CD8+CD45R+ subset, not CD8+CD45R-, exhibited the majority of suppressor activity after AMLR.
- Cytotoxic activity against alloantigens was present in both CD8+CD45R+ and CD8+CD45R- subsets.
- Treatment with anti-CD45R or anti-CD3 antibodies abolished the suppressor function of AMLR-activated CD8+ cells.
Conclusions:
- CD45R expression defines the major suppressor subpopulation within CD8+ cells after AMLR.
- Both CD45R and the CD3-T cell receptor (TCR) complex are critical for the suppressor function of AMLR-activated CD8+ cells.
- These findings highlight distinct roles for CD8+ cell subsets in immune regulation and contrast with mechanisms observed in CD4+ suppressor inducer cells.
Abstract:
In the present study, we have investigated the molecular basis for immunoregulatory function of CD8 cells after autologous mixed lymphocyte reaction (AMLR) activation. We demonstrated that the CD8+CD45R+ but not the CD8+CD45R- subset of cells was a subpopulation, with the majority of suppressor activity after AMLR activation. In contrast, cytotoxic activity against alloantigens resided in both the CD8+CD45R+ and CD8+CD45R- subsets of cells. Importantly, the treatment of AMLR-activated CD8 cells with anti-CD45R antibody or anti-CD3 antibody abolished the suppressor function of these cells, which contrasts with earlier studies showing that treatment of AMLR activated CD4 suppressor inducer cells could be blocked with anti-CD45R but not with anti-CD3 antibody. The results suggest that the CD45R antigen as well as the CD3-T cell receptor (TCR) complex have an important role in the suppressor function of AMLR-activated cells.
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