A soluble survival signal from CD14+ cells and its possible role in the pathogenesis of rheumatoid arthritis

Persistent Link:
http://hdl.handle.net/10150/279901
Title:
A soluble survival signal from CD14+ cells and its possible role in the pathogenesis of rheumatoid arthritis
Author:
Tang, Xiaolei
Issue Date:
2001
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Since macrophages play an important role in T cell activation, we investigated the role of CD14+ cells in T cell activation, proliferation and activation-induced cell death (AICD). Using PHA for activation, it was found that CD14+ cell depletion resulted in significantly greater AICD, decreased lymphocyte growth and increased IL-2 secretion. Lymphocyte activation was delayed as defined by CD69 and CD25 expression. ³H-TdR-incorporation was reduced in proportion to the percentage of AICD in the cultures. Addition of supernatants from activated CD14+ cells to CD14+ cell-depleted mononuclear cell cultures reversed the effects on AICD, IL-2 secretion and lymphocyte growth. Supernatants from TNF-α matured dendritic cells demonstrated the same activity as the CD14 cocktails. These data suggested a soluble survival signal from CD14+ cells that prevented apoptosis, maintaining an active immune response. Further studies demonstrated that depletion of CD14+ cells in rheumatoid arthritis (RA) patients resulted in greater AICD, decreased lymphocyte proliferation and even higher secretion of IL-2 compared with normal control subjects. While the CD14+ cell percentage in RA was not significantly higher than that in the age/sex-matched healthy controls, CD14 supernatants from RA showed a significantly greater protective effect on AICD. Data analysis revealed that CD14 supernatants supported the survival of activated lymphocytes in RA. These data underscored the importance of the soluble survival signal in the homeostasis of the immune system and in the pathogenesis of RA. The analysis of apoptotic cells showed that most of the apoptotic cells bore activation antigen CD69 and T cell antigen CD3, suggesting that most of the apoptotic cells were activated T lymphocytes. The soluble signal was also investigated. The CD14 cocktails contain IL-1β, TNF-α, TGF-β and IL-6, but not IL-12, or IL-15. Depletion assays using a panning method followed by blocking of residual IL-1β and TNF-α with corresponding monoclonal antibodies had no effect on the active AICD protection. As TGF-β was found in the culture medium containing 10% FBS, TGF-β might not be an active factor in the CD14 cocktails. Because the CD14 cocktails did not contain IL-12 or IL-15, these two cytokines were not the active factors either.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Health Sciences, Pathology.; Health Sciences, Immunology.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Microbiology and Immunology
Degree Grantor:
University of Arizona
Advisor:
Yocum, David E.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleA soluble survival signal from CD14+ cells and its possible role in the pathogenesis of rheumatoid arthritisen_US
dc.creatorTang, Xiaoleien_US
dc.contributor.authorTang, Xiaoleien_US
dc.date.issued2001en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractSince macrophages play an important role in T cell activation, we investigated the role of CD14+ cells in T cell activation, proliferation and activation-induced cell death (AICD). Using PHA for activation, it was found that CD14+ cell depletion resulted in significantly greater AICD, decreased lymphocyte growth and increased IL-2 secretion. Lymphocyte activation was delayed as defined by CD69 and CD25 expression. ³H-TdR-incorporation was reduced in proportion to the percentage of AICD in the cultures. Addition of supernatants from activated CD14+ cells to CD14+ cell-depleted mononuclear cell cultures reversed the effects on AICD, IL-2 secretion and lymphocyte growth. Supernatants from TNF-α matured dendritic cells demonstrated the same activity as the CD14 cocktails. These data suggested a soluble survival signal from CD14+ cells that prevented apoptosis, maintaining an active immune response. Further studies demonstrated that depletion of CD14+ cells in rheumatoid arthritis (RA) patients resulted in greater AICD, decreased lymphocyte proliferation and even higher secretion of IL-2 compared with normal control subjects. While the CD14+ cell percentage in RA was not significantly higher than that in the age/sex-matched healthy controls, CD14 supernatants from RA showed a significantly greater protective effect on AICD. Data analysis revealed that CD14 supernatants supported the survival of activated lymphocytes in RA. These data underscored the importance of the soluble survival signal in the homeostasis of the immune system and in the pathogenesis of RA. The analysis of apoptotic cells showed that most of the apoptotic cells bore activation antigen CD69 and T cell antigen CD3, suggesting that most of the apoptotic cells were activated T lymphocytes. The soluble signal was also investigated. The CD14 cocktails contain IL-1β, TNF-α, TGF-β and IL-6, but not IL-12, or IL-15. Depletion assays using a panning method followed by blocking of residual IL-1β and TNF-α with corresponding monoclonal antibodies had no effect on the active AICD protection. As TGF-β was found in the culture medium containing 10% FBS, TGF-β might not be an active factor in the CD14 cocktails. Because the CD14 cocktails did not contain IL-12 or IL-15, these two cytokines were not the active factors either.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectHealth Sciences, Pathology.en_US
dc.subjectHealth Sciences, Immunology.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineMicrobiology and Immunologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorYocum, David E.en_US
dc.identifier.proquest3031425en_US
dc.identifier.bibrecord.b42311391en_US
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