Related Experiment Video
Updated: Aug 14, 2026

An Optimized Method for Isolating and Expanding Invariant Natural Killer T Cells from Mouse Spleen
Published on: October 29, 2015
Itk is not essential for CD28 signaling in naive T cells
1Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Abstract:
Itk, a member of the Tec family of tyrosine kinases, is critical for TCR signaling, leading to the activation of phospholipase C gamma1. Early biochemical studies performed in tumor cell lines also implicated Itk in CD28 signaling. These data were complemented by functional studies on primary Itk-/- T cells that suggested a negative role for Itk in CD28 signaling. In this report, we describe a thorough analysis of CD28-mediated responses in T cells lacking Itk. Using purified naive CD4+ T cells from Itk-/- mice, we examine a range of responses dependent on CD28 costimulation. We also analyze Akt and glycogen synthase kinase-3beta phosphorylation in response to stimulation of CD28 alone. Overall, these experiments demonstrate that CD28 signaling, as well as CD28-mediated costimulation of TCR signaling, function efficiently in the absence of Itk. These findings indicate that Itk is not essential for CD28 signaling in primary naive CD4+ T cells.
Insights
The Tec family tyrosine kinase, Itk, is not essential for CD28 signaling in T cells. Studies show CD28 costimulation and signaling function effectively even without Itk in primary naive CD4+ T cells.
Area of Science:
- Immunology
- Molecular Biology
- Cell Signaling
Background:
- The Tec family tyrosine kinase, Itk, plays a known role in T cell receptor (TCR) signaling.
- Previous studies suggested a potential role for Itk in CD28 signaling, with some data indicating a negative regulatory function.
Purpose of the Study:
- To thoroughly investigate the role of Itk in CD28-mediated responses in primary T cells.
- To determine if Itk is essential for CD28 signaling and costimulation of TCR signaling.
Main Methods:
- Analysis of CD28-mediated responses in naive CD4+ T cells from Itk knockout (Itk-/-) mice.
- Examination of Akt and glycogen synthase kinase-3beta phosphorylation upon CD28 stimulation alone.
Main Results:
- CD28 signaling functions efficiently in the absence of Itk.
- CD28-mediated costimulation of TCR signaling is not impaired in Itk-/- T cells.
- Akt and GSK-3beta phosphorylation downstream of CD28 occurs normally without Itk.
Conclusions:
- Itk is not essential for CD28 signaling in primary naive CD4+ T cells.
- The findings challenge previous implications of Itk in CD28 signaling pathways.
Related Concept Videos
Inhibition of Cdk Activity
Role Of Notch Signalling In Intestinal Stem Cell Renewal
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Cells of the Innate Immune Response
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...
T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Cytotoxic 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...

