Mature resting Ly6C(high) natural killer cells can be reactivated by IL-15

Ai Omi1, Yutaka Enomoto, Tsuyoshi Kiniwa

  • 1Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.

Insights

Mature natural killer (NK) cells exhibit plasticity, with Ly6C(high) NK cells representing a resting subset that can be activated to Ly6C(low) effector cells. This plasticity is crucial for mounting effective immune responses during infection.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Mature natural killer (NK) cells display heterogeneity in cell surface molecule expression, but the functional implications of these subsets are not fully elucidated.
  • Understanding NK cell heterogeneity is key to comprehending their roles in immune surveillance and response.

Purpose of the Study:

  • To investigate the functional differences and physiological roles of distinct NK cell subsets.
  • To characterize the Ly6C(low) and Ly6C(high) NK cell subsets in C57BL/6 mice.

Main Methods:

  • Flow cytometry to identify and sort Ly6C(low) and Ly6C(high) NK cell subsets.
  • Assessment of cytokine production (IFN-γ) and cytotoxic potential (granzyme B).
  • Adoptive transfer experiments and in vitro/in vivo stimulation with IL-15, polyI:C, and CpG.

Main Results:

  • C57BL/6 murine NK cells can be divided into Ly6C(low) and Ly6C(high) subsets based on Ly6C expression.
  • Ly6C(high) NK cells are characterized by lower IFN-γ and granzyme B production and reduced proliferative capacity, indicating a resting state.
  • Ly6C(high) NK cells are derived from Ly6C(low) NK cells in vivo and can be activated to Ly6C(low) effector cells upon IL-15 stimulation, both in vitro and in vivo.

Conclusions:

  • Mature NK cells exhibit significant plasticity, with Ly6C(high) cells serving as a reservoir of resting cells.
  • This plasticity allows for a rapid and robust NK cell response upon encountering inflammatory stimuli like IL-15.
  • The Ly6C(high) to Ly6C(low) transition is a critical mechanism for effective immune responses to infections.

Related Concept Videos

Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
8.3K
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
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...
7.0K
Cells of the Adaptive Immune Response01:23

Cells of the Adaptive Immune Response

The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
6.8K
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
13.6K
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
3.2K
Immune Surveillance by NK Cells and Phagocytes01:25

Immune Surveillance by NK Cells and Phagocytes

Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
7.2K