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CD43 diminishes susceptibility to T lymphocyte-mediated cytolysis
T A McFarland1, B Ardman, N Manjunath
1Department of Medicine, New England Medical Center Hospitals, Boston, MA 02111.
Insights
CD43, a protein on hematopoietic cells, protects them from T cell-mediated lysis. Reduced CD43 or its sialic acid content increases cell susceptibility to T lymphocyte attack.
Area of Science:
- Immunology
- Cell Biology
Background:
- CD43 is a sialoglycoprotein found on hematopoietic cells.
- CD43 influences cellular adhesion.
- The role of CD43 in cell-mediated lysis is not fully understood.
Purpose of the Study:
- To investigate the impact of CD43 expression on the susceptibility of T cells to lysis.
- To determine if CD43's adhesive properties affect cell-mediated cytotoxicity.
Main Methods:
- Comparison of CD43-positive and CD43-negative human T cell lines (CEM).
- Gene targeting to create CD43-negative cells.
- Transfection of HeLa cells to induce CD43 expression.
- Cytotoxicity assays using allospecific T cell lines and a CD8+ T cell clone.
Main Results:
- CD43-negative cells showed increased susceptibility to lysis by T cells.
- Induced CD43 expression on HeLa cells conferred resistance to lysis.
- The protective effect of CD43 was more significant in short-term assays.
- Sialic acid residues on CD43 were crucial for its protective function.
Conclusions:
- CD43 expression reduces susceptibility to T lymphocyte-mediated cytolysis.
- Diminished CD43 expression or incomplete sialylation may increase vulnerability to T cell attack.
- CD43 plays a role in protecting hematopoietic cells from immune surveillance.
Abstract:
CD43 is a major membrane sialoglycoprotein expressed by cells of hematopoietic origin. One property of CD43 is its ability to interfere with heterotypic and homotypic cellular adhesion. To determine whether CD43 expression can affect cell functions requiring intercellular adhesion, we compared a CD43-positive human T cell line (CEM) and its CD43-negative counterpart derived by gene targeting for susceptibility to cell-mediated lysis. CD43-negative CEM cells were more susceptible than CD43-positive cells to lysis by allospecific T cell lines derived from several donors. Induction of CD43 expression on transfected HeLa cells also imparted resistance to lectin-mediated lysis by a CD8+ T cell clone. The effect of CD43 expression on reducing susceptibility to lysis was more pronounced in short-term cytotoxicity assays and tended to disappear as the time of contact between the effector cell and its target increased. The enhanced susceptibility of CD43-negative cells to lysis was not associated with increased expression of adhesion molecules known to mediate antigen-independent cellular adhesion. Sialic acid residues on CD43 contributed to the CD43 protective effect. These results suggest that either diminished CD43 expression or incomplete sialylation may render hematopoietic cells more susceptible to T lymphocyte-mediated cytolysis.