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CDw60: a marker for human CD8+ T helper cells
1Institute for Immunology, University of Munich, Germany.
Insights
Researchers identified the CDw60 antigen on CD8+ T cells, distinguishing helper and cytotoxic/suppressor functions. This discovery aids in understanding immune cell roles and developing targeted therapies.
Area of Science:
- Immunology
- Cell Biology
- T cell subsets
Background:
- The CD8+ T cell subset includes cells with helper functions, but their specific phenotype has been unclear.
- Distinguishing between CD8+ T helper cells and those with cytotoxic/suppressor roles is crucial for immune response understanding.
Purpose of the Study:
- To identify a specific cell surface marker that distinguishes CD8+ T helper cells from CD8+ T cells with cytotoxic and suppressor functions.
- To characterize the functional properties of CD8+ T cell subsets defined by CDw60 expression.
Main Methods:
- Utilized CDw60 monoclonal antibodies (mAb) to identify the CDw60 antigen on human CD8+ T cells.
- Employed mAb-rosetting techniques for high-purity isolation of CDw60+CD8+ and CDw60-CD8+ cell populations.
- Assayed cytotoxic activity, B cell helper/suppressor functions, and cytokine production (IL-2, IL-4, interferon-gamma) of isolated subsets.
Main Results:
- CDw60+CD8+ cells exhibited helper activity for B cell differentiation, while CDw60-CD8+ cells showed suppressor capacity.
- Alloantigen-specific cytotoxic activity was exclusively found in the CDw60-CD8+ population.
- Both subsets produced IL-2; IL-4 was preferentially secreted by CDw60+CD8+ cells, and interferon-gamma by CDw60-CD8+ cells.
Conclusions:
- CDw60 expression on human CD8+ T cells serves as a reliable marker to differentiate between T helper and T cytotoxic/suppressor subsets.
- The CDw60 marker, in conjunction with others, can define CD8+ T cell subsets with distinct and reciprocal immune functions.
Abstract:
The existence of helper cells among the CD8+ T cell subset has been recognized for a long time. However, the phenotype of these cells has remained elusive. In this study, we provide evidence that the expression of the CDw60 antigen on human CD8+ T cell allows one to distinguish between CD8+ T helper cells and CD8+ T cells with cytotoxic and suppressor capacity. CDw60 monoclonal antibodies (mAb) recognize the 9-O-acetylated disialosyl group on ganglioside GD3 expressed on 20-40% of CD8+ cells. By use of the direct and indirect mAb-rosetting technique, we were able to isolate the CDw60+CD8+ and CDw60-CD8+ cells at high purity. The alloantigen-specific cytotoxic activity of CD8+ cells resided entirely in the CDw60- population. Helper and suppressor capacity of both CD8 subsets was assayed by the pokeweed mitogen-induced differentiation of B cells into immunoglobulin-secreting cells. These studies clearly indicate that the CDw60+CD8+ subset provided substantial help to B lymphocytes, whereas the CD8+ cells with the CDw60- phenotype were suppressing B cell differentiation. Both subsets produced similar amounts of interleukin 2 (IL-2) after stimulation with phytohemagglutinin. Activation with phorbol myristate acetate in combination with Ca-ionophore induced IL-4 secretion in both populations, but preferentially in the CDw60+ subset, whereas the vast majority of interferon gamma was produced by the CDw60-CD8+ cells. When used in combination with other markers, CDw60 may prove to be useful in defining CD8+ subsets with reciprocal functional activities.