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Journal article
Impaired T-cell responses to sphingosine-1-phosphate in HIV-1 infected lymph nodes
Blood, v 121(15), pp 2914-2922
11 Apr 2013
PMID: 23422746
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
S1P1 activity in human T cells can be reliably measured by assessing downstream signaling events induced upon S1P1 ligation.
S1P1 activity is impaired in T cells from HIV-1+ lymph nodes.
The determinants of HIV-1-associated lymphadenopathy are poorly understood. We hypothesized that lymphocytes could be sequestered in the HIV-1+ lymph node (LN) through impairments in sphingosine-1-phosphate (S1P) responsiveness. To test this hypothesis, we developed novel assays for S1P-induced Akt phosphorylation and actin polymerization. In the HIV-1+ LN, naïve CD4 T cells and central memory CD4 and CD8 T cells had impaired Akt phosphorylation in response to S1P, whereas actin polymerization responses to S1P were impaired dramatically in all LN maturation subsets. These defects were improved with antiretroviral therapy. LN T cells expressing CD69 were unable to respond to S1P in either assay, yet impaired S1P responses were also seen in HIV-1+ LN T cells lacking CD69 expression. Microbial elements, HIV-1, and interferon α – putative drivers of HIV-1associated immune activation all tended to increase CD69 expression and reduce T-cell responses to S1P in vitro. Impairment in T-cell egress from lymph nodes through decreased S1P responsiveness may contribute to HIV-1-associated LN enlargement and to immune dysregulation in a key organ of immune homeostasis.
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Details
- Title
- Impaired T-cell responses to sphingosine-1-phosphate in HIV-1 infected lymph nodes
- Creators
- Joseph C. Mudd - Case Western Reserve UniversityPatrick Murphy - Division of Infectious Diseases, Center for AIDS Research, andMaura Manion - Division of Infectious Diseases, Center for AIDS Research, andRobert Debernardo - Case Western Reserve UniversityJeffrey Hardacre - University Hospitals Cleveland Medical CenterJohn Ammori - University Hospitals Cleveland Medical CenterGareth A. Hardy - Department of Pathology andClifford V. Harding - Department of Pathology andGanapati H. Mahabaleshwar - Case Western Reserve UniversityMukesh K. Jain - Case Western Reserve UniversityJeffrey M. Jacobson - Drexel UniversityAri D. Brooks - Drexel UniversitySharon Lewis - Drexel UniversityTimothy W. Schacker - University of MinnesotaJodi Anderson - University of MinnesotaElias K. Haddad - Vaccine & Gene Therapy Institute of FloridaRafael A. Cubas - Vaccine & Gene Therapy Institute of FloridaBenigno Rodriguez - Division of Infectious Diseases, Center for AIDS Research, andScott F. Sieg - Division of Infectious Diseases, Center for AIDS Research, andMichael M. Lederman - Division of Infectious Diseases, Center for AIDS Research, and
- Publication Details
- Blood, v 121(15), pp 2914-2922
- Publisher
- American Society of Hematology
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Infectious Diseases (and HIV Medicine); Surgery
- Web of Science ID
- WOS:000321825700016
- Scopus ID
- 2-s2.0-84879429159
- Other Identifier
- 991019335242404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Hematology