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Updated: Aug 11, 2026
Immunostimulatory Agent Evaluation: Lymphoid Tissue Extraction and Injection Route-Dependent Dendritic Cell Activation
Published on: September 16, 2018
Co-stimulation and modulation of the ensuing immune response
C J Howard1, J C Hope, S A Stephens
1Institute for Animal Health, Compton, Near Newbury RG20 7NN, UK. chris.howard@bbsrc.ac.uk
Insights
Ruminant dendritic cells (DCs) influence immune responses. Two DC types, CD11a(+)/SIRPalpha(-) and CD11a(-)/SIRPalpha(+), show distinct cytokine profiles, impacting T cell bias and immune memory.
Area of Science:
- Immunology
- Cell Biology
- Veterinary Science
Background:
- Dendritic cells (DCs) are crucial for initiating immune responses, and their properties can lead to long-term immune effects.
- Ruminant afferent lymph DCs offer a unique model for studying ex vivo DC properties with broad implications.
- Previous research identified two cattle skin-draining DC populations with differing capacities to stimulate CD4 and CD8 T cells.
Purpose of the Study:
- To investigate the cytokine transcript expression differences between two distinct ruminant afferent lymph DC populations.
- To elucidate the functional roles of these DC subsets in T cell stimulation and immune response bias.
- To explore the involvement of SIRPalpha and CD26 molecules in DC function and T cell interaction.
Main Methods:
- Analysis of cytokine transcripts in isolated CD11a(+)/SIRPalpha(-) and CD11a(-)/SIRPalpha(+) DC populations.
- Assessment of T cell stimulation capacity, including CD4 and CD8 T cell responses.
- Investigation of co-stimulatory molecule expression (CD80, CD86, CD40) and SIRPalpha signaling pathways.
- Identification of other surface molecules like CD26 on specific DC subsets.
Main Results:
- CD11a(+)/SIRPalpha(-) DCs synthesized more IL-12, while CD11a(-)/SIRPalpha(+) DCs produced more IL-10.
- CD11a(+)/SIRPalpha(-) DCs failed to stimulate CD8 T cells due to an inability to synthesize IL-1alpha.
- SIRPalpha signaling, involving SHP-2 phosphatase, modulated TNFalpha secretion; CD26 was identified on SIRPalpha(-) DCs, potentially promoting Th1 bias.
Conclusions:
- Distinct cytokine profiles of ruminant DC subsets (IL-12 vs. IL-10) likely dictate the bias of T cell-mediated immune responses.
- The absence of IL-1alpha in CD11a(+)/SIRPalpha(-) DCs may explain their limited capacity to induce CD8 T cell responses.
- A proposed model suggests SIRPalpha(-) DCs promote Th1 responses, while SIRPalpha(+) DCs contribute to more balanced immunity.
Abstract:
As a consequence of the central role of dendritic cells (DC) in stimulating primary immune responses any bias in the response introduced by the DC has the potential for having a long-term effect on immunity. Examination and analysis of ruminant afferent lymph dendritic cells derived by cannulation allows studies on the properties of ex vivo DC that is not possible in humans and rodents and information can be derived from ruminants that has implications of generic relevance. Previous studies have identified two major populations of DC in afferent lymph draining the skin of cattle that differ in their capacity to stimulate CD4 and CD8 T cells. Differences in expression of cytokine transcripts have now been shown for the two types of DC. The CD11a(+)/SIRPalpha(-) population synthesised more IL-12, whilst the CD11a(-)/SIRPalpha(+) population produced more IL-10. This is likely to affect the bias of the immune response following presentation of antigen to T cells by one DC sub-population or the other. An inability to synthesise IL-1alpha was the reason for the failure of the CD11a(+)/SIRPalpha(-) DC to stimulate CD8 T cells. This property would potentially affect the induction of CD8 responses. Expression of the co-stimulatory molecules CD80, CD86 and CD40 appeared similar for both DC populations and not to relate to differences in function. A further examination of the SIRPalpha molecule on DC indicated that on cross-linking it was tyrosine phosphorylated and that it recruited the SHP-2 protein phosphatase. Associated with this was a blocking of TNFalpha secretion on exposure to LPS. The interaction of SIRPalpha with its ligand CD47 on T cells appeared to be an early event in the stimulation of T cells as binding of the ligand was reduced on activated T cells. CD26 was identified as another molecule expressed by the SIRPalpha(-) DC sub-population. This is reported to have an enzymatic activity on certain chemokines that could result in the promotion of a Th1 bias.A model is proposed that takes these observations into account in which SIRPalpha(-) DC would be expected to promote a Th1 biased response and the SIRPalpha(+) DC a more balanced one.
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