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PMID: 8690786 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A novel mechanism of glucocorticoid-induced immune suppression: the inhibiton of T cell-mediated terminal maturation of a murine dendritic cell line.

The Journal of clinical investigation ·Vol. 98 ·No. 1 ·1996-07-01 ·Pages 142-7

Kitajima T, Ariizumi K, Bergstresser PR, Takashima A

Abstract

Working with the murine epidermal-derived dendritic cell (DC) line XS52, we have observed previously that antigen-specific interaction with T cells stimulates their "terminal maturation" into fully professional DC. In this study we examined the impact of dexamethasone (DEX) on this T cell-induced event. When added to cocultures of XS52 DC and the KLH-specific Th1 clone HDK-1 in the presence of antigen, DEX at relatively low concentrations (10(-9)-10(-7) M) prevented substantially or completely each of the changes that typify terminal maturation, including (a) secretion of relatively large amounts of IL-1beta, IL-6, and TNFalpha; (b) loss of CD115 (colony-stimulating factor-1 receptor) expression and proliferative responsiveness to colony-stimulating factor-1; and (c) elevated expression of CD86 (B7-2). XS52 cells also underwent terminal maturation upon exposure to lipopolysaccharide alone, and DEX also inhibited effectively each of the same changes, indicating that DC can serve as the direct target of DEX. By contrast, DEX inhibited XS52 DC-stimulated IL-2 secretion by HDK-1 T cells, but not other changes that accompany T cell activation, including the secretion of IFNgamma and TNFalpha and the elevated expression of CD25, CD28, and CD44. These results reveal a new immunosuppressive mechanism of glucocorticoid action, that is, direct inhibition of T cell-mediated terminal maturation by DC.

MeSH Terms
Animals Antigens, CD/biosynthesis Cell Differentiation Cell Line Cytokines/metabolism Dendritic Cells/immunology Dexamethasone/pharmacology Dose-Response Relationship, Drug Glucocorticoids/pharmacology Immunosuppression Therapy Immunosuppressive Agents/pharmacology Mice T-Lymphocytes/immunology
Chemicals
Antigens, CD Cytokines Glucocorticoids Immunosuppressive Agents Dexamethasone
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kitajima T
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Ariizumi K
Bergstresser P R
Takashima A
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI118759
Published
1996-07-01
Pages
142-7
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC507410
Subset
IM
Grants
NIAMS NIH HHS · R01 AR35068 · United States
NIAMS NIH HHS · R01 AR40042 · United States
NIAMS NIH HHS · R01 AR41150 · United States
External Links
PubMed source DOI: 10.1172/JCI118759 PMC Full Text View journal details
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