NKG2D is a costimulatory receptor for human naive CD8+ T cells
Kerima Maasho1, Jessica Opoku-Anane, Alina I Marusina
1Receptor Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852-1742, USA.
Insights
NKG2D acts as a costimulatory receptor in human CD8+ T cells, enhancing their proliferation and type 1 immune response. Homeostatic cytokines like IL-7 and IL-15 further boost this effect.
Area of Science:
- Immunology
- Cell Biology
- T cell Activation
Background:
- NKG2D expression differs between human (all alpha beta CD8+ T cells) and mouse (activated/memory CD8+ T cells).
- NKG2D is a receptor involved in immune surveillance and T cell responses.
Purpose of the Study:
- To investigate the role of NKG2D in the priming of human naive CD8+ T cells.
- To determine if NKG2D acts as a costimulatory receptor during T cell activation.
Main Methods:
- Purification of human naive CD8+ T cells.
- Stimulation via T cell receptor (TCR) and measurement of calcium (Ca2+) mobilization and proliferation.
- Analysis of effector cell phenotype and cytokine production (IFN-gamma, TNF-alpha).
- Assessment of NKG2D ligand expression and NKG2D downregulation.
- Evaluation of the effects of homeostatic cytokines (IL-7, IL-15, IL-2) on T cell proliferation and NKG2D expression.
Main Results:
- NKG2D functions as a costimulatory receptor, enhancing TCR-induced Ca2+ mobilization and proliferation of human naive CD8+ T cells.
- Effector cells generated exhibit a type 1 phenotype, producing high levels of IFN-gamma and TNF-alpha.
- NKG2D ligands are expressed on proliferating cells, leading to NKG2D downregulation.
- IL-7 and IL-15 enhance proliferation and counteract NKG2D downregulation more effectively than IL-2.
Conclusions:
- NKG2D plays a regulatory role in the priming of human naive CD8+ T cells.
- NKG2D signaling offers a potential mechanism to potentiate and direct immune responses.
- The findings highlight the importance of homeostatic cytokines in maintaining NKG2D function during T cell activation.
Abstract:
In humans, all alpha beta CD8+ T cells express NKG2D, but in mouse, it is only expressed by activated and memory CD8+ T cells. We purified human naive CD8+ T cells to show that NKG2D serves as a costimulatory receptor for TCR induced Ca2+ mobilization and proliferation. The resulting effector cells are skewed toward a type 1 phenotype and produce high levels of IFN-gamma and TNF-alpha. NKG2D ligands, MHC class I chain-related (MIC)A, MICB, and UL16-binding proteins are expressed on the proliferating cells and NKG2D is down-regulated. The addition of the homeostatic cytokines IL-7 and IL-15 to the culture medium not only enhances proliferation but also counteracts the down-regulation of NKG2D, more so than the addition of IL-2. These results indicate that NKG2D can regulate the priming of human naive CD8+ T cells, which may provide an alternative mechanism for potentiating and channeling the immune response.
Related Concept Videos
01:31Immunoglobulin-like Cell Adhesion Molecules
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
01:25Immune Surveillance by NK Cells and Phagocytes
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
01:22T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
01:27Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...