Regulation of Asymmetric Division by Atypical Protein Kinase C Influences Early Specification of CD8+ T Lymphocyte Fates
Year: 2016
Type: article
Abstract: Naïve CD8(+) T lymphocytes responding to microbial pathogens give rise to effector T cells that provide acute defense and memory T cells that provide long-lived immunity. Upon activation, CD8(+) T lymphocytes can undergo asymmetric division, unequally distributing factors to the nascent daughter cells that influence their eventual fate towards the effector or memory lineages. Individual loss of either atypical protein kinase C (aPKC) isoform, PKCζ or PKCλ/ι, partially impairs asymmetric divisions and increases CD8(+) T lymphocyte differentiation toward a long-lived effector fate at the expense of memory T cell formation. Here, we show that deletion of both aPKC isoforms resulted in a deficit in asymmetric divisions, increasing the proportion of daughter cells that inherit high amounts of effector fate-associated molecules, IL-2Rα, T-bet, IFNγR, and interferon regulatory factor 4 (IRF4). However, unlike CD8(+) T cells deficient in only one aPKC isoform, complete loss of aPKC unexpectedly increased CD8(+) T cell differentiation toward a short-lived, terminal effector fate, as evidenced by increased rates of apoptosis and decreased expression of Eomes and Bcl2 early during the immune response. Together, these results provide evidence for an important role for asymmetric division in CD8(+) T lymphocyte fate specification by regulating the balance between effector and memory precursors at the initiation of the adaptive immune response.
Source: Scientific Reports
DOI: 10.1038/srep19182
Institutions: University of California San Diego, Yokohama City University
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Funders: Howard Hughes Medical Institute, National Institutes of Health, University of California, San Diego, Japan Society for the Promotion of Science, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke
Awards: The UCSD Digestive Diseases Research Development Center, G3033040839, Role of atypical Protein Kinase C in Inflammatory Bowel Disease, G4915581616, Understanding the Basis for Cellular Diversity During Adaptive Immunity, G5387381669, Regulation and Function of Polarity and Asymmetric Cell Division in Immunity, University of California San Diego Neuroscience Microscopy Imaging Core, G639426234, G705904519, Training Grant in Gastroenterology, G9000255603, Asymmetric T cell division initiating adaptive immunity and colitis
OpenAlex ID: W2411123281