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Updated: Jul 6, 2026
Measurement of T Cell Alloreactivity Using Imaging Flow Cytometry
Published on: April 19, 2017
CD44 mobilization in allogeneic dendritic cell-T cell immunological synapse plays a key role in T cell activation
Venkatesh L Hegde1, Narendra P Singh, Prakash S Nagarkatti
1Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
Insights
CD44 clustering at the immunological synapse (IS) is crucial for T cell activation. This study reveals CD44
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- CD44 is a cell adhesion and signaling molecule involved in various biological processes.
- The precise role of CD44 in the formation and function of the immunological synapse (IS) is not fully understood.
- Previous assumptions suggested large molecules like CD44 are excluded from the IS.
Purpose of the Study:
- To investigate the role of CD44 in dendritic cell (DC)-T cell interactions.
- To determine if CD44 localizes to the IS during DC-T cell contact.
- To elucidate the functional significance of CD44 in T cell activation.
Main Methods:
- Utilized an allogeneic DC-T cell interaction model.
- Employed CD44-deficient mice for both DCs and T cells.
- Analyzed CD44 localization, conjugate formation, and IS composition (phosphotyrosine, PKC-theta).
- Assessed T cell proliferation and cytokine production (IL-2, IFN-gamma).
- Confirmed findings in an antigen-specific syngeneic model.
Main Results:
- CD44 clusters at the T cell-mature DC interface and co-localizes with lipid rafts at the IS.
- CD44 on both DCs and T cells is essential for forming tight DC-T cell conjugates.
- CD44 deficiency on DCs, but not T cells, impairs functional IS formation.
- CD44-deficient DCs induce reduced T cell proliferation and cytokine production (IL-2, IFN-gamma).
Conclusions:
- CD44 is recruited to the IS during DC-T cell interactions, challenging previous notions of exclusion.
- CD44 plays a critical role in the formation of stable DC-T cell conjugates and functional IS.
- CD44 on dendritic cells is vital for initiating subsequent T cell activation and cytokine release.
Abstract:
CD44 is involved in several biological processes owing to its dual role as a cell adhesion and signaling molecule. In an allogeneic dendritic cell (DC)-T cell interaction model, we show here that CD44 gets clustered at the contact between T cells with mature but not immature DCs. Also, CD44 colocalized with lipid rafts at the immunological synapse (IS). Using DCs or T cells derived from CD44-deficient mice, we observed that the presence of CD44 on DCs and T cells is important for the formation of DC-T cell tight conjugates. However, deficiency of CD44 on DCs but not T cells affected the functional IS, as indicated by decreased phosphotyrosine and protein kinase C-theta enrichment at the synapse. Also, CD44-deficient DCs induced significantly decreased proliferation as well as IL-2 and IFN-gamma production from allogeneic T cells. The polarization of CD44 at the synapse was also noted in an antigen (OVA)-specific, syngeneic DC-T cell interaction using OVA-specific T cells derived from OT-II mice. It was believed that large molecules such as CD44 were excluded from the IS. Results presented here show for the first time that CD44 is recruited to the IS during allogeneic DC and T cell interactions and plays an important role in subsequent T cell activation.
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