NKG2D signaling certifies effector CD8 T cells for memory formation
Autor: | Kushal Prajapati, Brianna Burke, Lourdes Plaza-Rojas, Cynthia Perez, Nancy J. Zeleznik-Le, José A. Guevara-Patiño |
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Rok vydání: | 2019 |
Předmět: |
Cancer Research
T cell Immunology Melanoma Experimental Mice Transgenic CD8 T cells chemical and pharmacologic phenomena CD8-Positive T-Lymphocytes Mouse models Immunological memory lcsh:RC254-282 NKG2D 03 medical and health sciences 0302 clinical medicine Immune system medicine Animals Immunology and Allergy Cytotoxic T cell Memory formation Pharmacology Chemistry Effector T-cell receptor hemic and immune systems lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Acquired immune system Cell biology Mice Inbred C57BL medicine.anatomical_structure Oncology NK Cell Lectin-Like Receptor Subfamily K 030220 oncology & carcinogenesis Ribosomal protein s6 Molecular Medicine Immunologic Memory Research Article 030215 immunology |
Zdroj: | Journal for ImmunoTherapy of Cancer, Vol 7, Iss 1, Pp 1-14 (2019) Journal for Immunotherapy of Cancer |
ISSN: | 2051-1426 |
DOI: | 10.1186/s40425-019-0531-2 |
Popis: | Background The development of memory responses is an evolutionary function of the adaptive immune system. We propose that for the immune system to populate the memory compartment with the best-suited CD8 T cells it utilizes a process of certification or molecular accreditation mediated through Natural Killer Group 2D (NKG2D). This process of certification assures that the memory compartment is filled with CD8 T cells that have demonstrated their ability to kill their cognate targets through a two-step process that utilizes T cell receptor (TCR) and NKG2D signaling. Methods One week after immunization with peptide-pulsed dendritic cells, NKG2D signaling was transiently blocked in vivo with a single injection of neutralizing antibodies. Under such conditions, we determined the importance of NKG2D signaling during the effector phase for memory formation without compromising NKG2D signaling at the memory phase. Both open (polyclonal) and closed (monoclonal) CD8 T cell repertoires were studied. Results We show that signaling through NKG2D mediated this certification. Temporary blockade of NKG2D signaling during the effector phase resulted in the formation of highly defective memory CD8 T cells characterized by altered expression of the ribosomal protein S6 and epigenetic modifiers, suggesting modifications in the T cell translational machinery and epigenetic programming. Finally, these uncertified memory cells were not protective against a B16 tumor challenge. Conclusion Signaling through NKG2D during the effector phase (certification) favors the development of functional memory CD8 T cells, a previously undescribed role for NKG2D. Temporary blockade of NKG2D signaling during the effector phase results in the formation of highly defective memory CD8 T cells potentially by affecting the expression of the ribosomal protein S6 and epigenetic modifiers, suggesting alterations in T cell translational machinery and epigenetic programming. Electronic supplementary material The online version of this article (10.1186/s40425-019-0531-2) contains supplementary material, which is available to authorized users. |
Databáze: | OpenAIRE |
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