CD40/CD154 Interactions Are Required for the Optimal Maturation of Skin-derived APCs and the Induction of Helminth-specific IFN-gamma but Not IL-4

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2006 Aug 22

PMID 16920960

Citations 6

Authors

James P Hewitson

Gavin R Jenkins

Paul A Hamblin

Adrian P Mountford

Affiliations

Soon will be listed here.

Abstract

The mechanisms through which Schistosoma mansoni larvae induce Th1 rather than Th2 immune responses are not well understood. In this study, using CD154-/- mice exposed to radiation-attenuated S. mansoni larvae, we demonstrate roles for CD154/CD40 in the activation of skin-derived APCs and the development of Th1 cells in the skin-draining lymph nodes (sdLN). The presence of CD154 was important for optimal IL-12p40 and essential for Ag-specific IFN-gamma, but CD154 expression by wild-type CD4- cells was insufficient to rescue recall responses of CD4+ cells from CD154-/- mice. This defect is probably due to impaired CD40-dependent IL-12 production in vivo, because administration of anti-CD40 Ab, or rIL-12, restored IFN-gamma production by sdLN cells from CD154-/- mice. CD154 ligation of CD40 was not required for the migration of skin-derived APCs, but did have a limited role in their maturation (increased MHC II and CD86). Unexpectedly, although CD4 cells from CD154-/- mice were deficient in their ability to produce IFN-gamma, they produced significant amounts of IL-4 and IL-5 in the presence of skin-derived APCs from wild-type and CD154-/- mice. Thus, in contrast to IFN-gamma, the production of Th2-associated cytokines is (in this model) independent of CD154. We conclude that whereas the priming of Th1 responses soon after exposure to schistosome larvae is completely CD40/CD154 dependent, IL-4, IL-5, and IL-13 are independent of CD154, suggesting a dichotomy in the specific mechanisms that induce these cytokines by CD4+ cells in the sdLN.

Citing Articles

CD4 T-cell hyporesponsiveness induced by schistosome larvae is not dependent upon eosinophils but may involve connective tissue mast cells.

Prendergast C, Sanin D, Mountford A Parasite Immunol. 2015; 38(2):81-92.

PMID: 26679416 PMC: 4744672. DOI: 10.1111/pim.12300.

CD4+ T cell hyporesponsiveness after repeated exposure to Schistosoma mansoni larvae is dependent upon interleukin-10.

Prendergast C, Sanin D, Cook P, Mountford A Infect Immun. 2015; 83(4):1418-30.

PMID: 25624353 PMC: 4363412. DOI: 10.1128/IAI.02831-14.

Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells.

Cook P, Aynsley S, Turner J, Jenkins G, van Rooijen N, Leeto M PLoS Pathog. 2011; 7(3):e1001323.

PMID: 21445234 PMC: 3060168. DOI: 10.1371/journal.ppat.1001323.

CD40 and the immune response to parasitic infections.

Subauste C Semin Immunol. 2009; 21(5):273-82.

PMID: 19616968 PMC: 2758065. DOI: 10.1016/j.smim.2009.06.003.

In the absence of CD154, administration of interleukin-12 restores Th1 responses but not protective immunity to Schistosoma mansoni.

Hewitson J, Hamblin P, Mountford A Infect Immun. 2007; 75(7):3539-47.

PMID: 17485453 PMC: 1932915. DOI: 10.1128/IAI.00252-07.

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