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Updated: Aug 11, 2026
Generation of Human CD40-activated B cells
Published on: October 17, 2009
Systemic treatment with anti-CD40 antibody stimulates Langerhans cell migration from the skin
S Jolles1, J Christensen, M Holman
1Division of Cellular Immunology, The National Institute for Medical Research, Mill Hill, London, UK. sjolles@nimr.mrc.ac.uk
Insights
Systemic anti-CD40 antibody treatment prompts epidermal Langerhans cells (LCs) migration from skin. This immune cell migration is distinct from their maturation, impacting cutaneous immune responses and potential therapeutic applications.
Area of Science:
- Immunology
- Dermatology
- Cell Biology
Background:
- Epidermal Langerhans cells (LCs) are crucial for initiating skin immune responses.
- LC maturation and migration to lymph nodes are vital for antigen presentation to T cells.
- CD40, a costimulatory molecule, is expressed on LCs and skin keratinocytes.
Purpose of the Study:
- To investigate the effect of systemic anti-CD40 antibody treatment on epidermal LC migration and function.
- To determine if CD40 stimulation influences LC maturation and immunostimulatory capacity.
Main Methods:
- Mice were treated systemically with an anti-CD40 antibody.
- LC numbers, morphology, and expression of Class II, ICAM-1, and CD86 were analyzed.
- Epidermal LCs were isolated and tested for their ability to stimulate allogeneic mixed leucocyte reactions (MLR).
Main Results:
- Anti-CD40 treatment significantly reduced epidermal LC numbers by 70% within 7 days, with recovery by day 21.
- LCs showed morphological changes and up-regulated Class II and ICAM-1 expression, but minimal CD86 changes.
- Despite altered surface markers, epidermal LCs from treated mice were poor stimulators in MLR, similar to controls.
Conclusions:
- CD40 stimulation effectively drives LC migration out of the epidermis.
- This migration is independent of the maturation of LC immunostimulatory function within the skin.
- Findings have implications for anti-CD40 antibody therapies used as adjuvants or in treating immune deficiencies.
Abstract:
Epidermal Langerhans cells (LCs) play a pivotal role in the initiation of cutaneous immune responses. The maturation of LCs and their migration from the skin to the T cell areas of draining lymph nodes are essential for the delivery and presentation of antigen to naïve T cells. CD40, which acts as a costimulatory molecule, is present on LCs and the basal layer of keratinocytes in the skin. We show here that systemic treatment of mice with anti-CD40 antibody stimulates the migration of LCs out of the epidermis with a 70% reduction in LC numbers after 7 days, although changes in LC morphology are detectable as early as day 3. LC numbers in the epidermis returned to 90% of normal by day 21. As well as morphological changes, LC showed up-regulated levels of Class II and ICAM-1, with only minimal changes in CD86 expression 3 days following anti-CD40 treatment. Despite increased levels of Class II and ICAM-1, epidermal LC isolated from anti-CD40 treated mice were poor stimulators of a unidirectional allogeneic mixed leucocyte reaction (MLR), as were epidermal LC isolated from control mice. These results indicate that CD40 stimulation is an effective signal for LC migration, distinct from maturation of immunostimulatory function in the epidermis, which is not altered. These observations may have important implications for the mechanism of action of agonistic anti-CD40 antibodies, which have been used as an adjuvant in models of infection and experimental tumours and the primary immunodeficiency Hyper IgM syndrome caused by deficiency of CD40 ligand.
