Journal article
Activation-induced CD154 expression abrogates tolerance induced by apoptotic cells
The Journal of immunology (1950), Vol.183(10), pp.6114-6123
11/15/2009
DOI: 10.4049/jimmunol.0901676
PMCID: PMC2783861
PMID: 19841180
Abstract
The decision to generate a productive immune response or tolerance often depends on the context in which T cells first see Ag. Using a classical system of tolerance induction, we examined the immunological consequence of Ag encountered in the presence of naïve or activated apoptotic cells. Naïve apoptotic cells induced tolerance when injected i.v.; however, previously activated apoptotic cells induced immunity. Further analysis revealed a key role for CD154, as tolerance resulted after i.v. injection of either naïve or activated apoptotic CD154
−/−
T cells, while co-injection of an agonistic anti-CD40 mAb with naïve apoptotic T cells induced robust immunity. DC fed activated apoptotic T cells
in vitro
produced IL-12p40 in a CD154-dependent manner, and the use of IL-12p40
−/−
mice or mAb-mediated neutralization of IL-12 revealed a link between CD154, IL-12, and the ability of activated apoptotic T cells to induce immunity rather than tolerance. Collectively these results show that CD154 expression on apoptotic T cells can determine the outcome of an immune response to Ag recognized within the context of the apoptotic cells, and suggest the balance between naïve and activated apoptotic T cells may dictate whether a productive immune response is encouraged.
Details
- Title: Subtitle
- Activation-induced CD154 expression abrogates tolerance induced by apoptotic cells
- Creators
- Prajwal Gurung - Department of Urology, University of Iowa, Iowa City, IA 52242Tamara A Kucaba - Department of Urology, University of Iowa, Iowa City, IA 52242Thomas A Ferguson - Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110Thomas S Griffith - Department of Urology, University of Iowa, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.183(10), pp.6114-6123
- DOI
- 10.4049/jimmunol.0901676
- PMID
- 19841180
- PMCID
- PMC2783861
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 11/15/2009
- Academic Unit
- Infectious Diseases; Internal Medicine
- Record Identifier
- 9984094533002771
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