Human cytomegalovirus-induced immunosuppression

Relationship to tumor necrosis factor-dependent release of arachidonic acid and prostaglandin E2 in human monocytes

Mostafa A. Nokta, Mahmound I. Hassan, Kimberly Loesch, Richard B Pollard

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Cytomegalovirus (CMV) has been associated with immunesuppression. Previously CMV was reported to interfere with signal transduction pathways in T cells. In this report the mechanisms underlying CMV-mediated immunosuppression were examined. Supernatants of CMV (Strains C-87, AD-169)-infected primary human monocyte (MO) cultures inhibited mitogenic T cell proliferative responses by > 95%. The inhibitory activity was observed 24 h through day 7 postinfection. The infection of MO was associated with a sustained elevation of intracellular levels of cAMP and the release of arachidonic acid (AA) and its metabolite PGE2 (activator of adenylate cyclase) in culture supernatants. The AA release was incidentally associated with TNF-α production. Monoclonal antibodies to TNF-α and pentoxyphylline (inhibitor of TNF synthesis) inhibited both AA and PGE2 release. The release of AA required protein synthesis and occurred under conditions consistent with the expression of CMV immediate early genes. Treatment of MO cultures at time of infection with 100 μM indomethacin or 1 μg of TNF-α mAb abolished the CMV-induced T cell inhibitory activity of the supernatants by 100%. These data suggest that TNF dependent release of AA and PGE2 contributes to CMV-induced immunosuppression.

Original languageEnglish (US)
Pages (from-to)2635-2641
Number of pages7
JournalJournal of Clinical Investigation
Volume97
Issue number11
StatePublished - Jun 1 1996
Externally publishedYes

Fingerprint

Cytomegalovirus
Dinoprostone
Arachidonic Acid
Immunosuppression
Monocytes
Tumor Necrosis Factor-alpha
T-Lymphocytes
Immediate-Early Genes
Infection
Adenylyl Cyclases
Indomethacin
Signal Transduction
Monoclonal Antibodies
Proteins

Keywords

  • Cytokines
  • Immunosuppression
  • PGE
  • TNF-α
  • Viruses

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Human cytomegalovirus-induced immunosuppression : Relationship to tumor necrosis factor-dependent release of arachidonic acid and prostaglandin E2 in human monocytes. / Nokta, Mostafa A.; Hassan, Mahmound I.; Loesch, Kimberly; Pollard, Richard B.

In: Journal of Clinical Investigation, Vol. 97, No. 11, 01.06.1996, p. 2635-2641.

Research output: Contribution to journalArticle

@article{11114e062ae148b09377961ed08790e9,
title = "Human cytomegalovirus-induced immunosuppression: Relationship to tumor necrosis factor-dependent release of arachidonic acid and prostaglandin E2 in human monocytes",
abstract = "Cytomegalovirus (CMV) has been associated with immunesuppression. Previously CMV was reported to interfere with signal transduction pathways in T cells. In this report the mechanisms underlying CMV-mediated immunosuppression were examined. Supernatants of CMV (Strains C-87, AD-169)-infected primary human monocyte (MO) cultures inhibited mitogenic T cell proliferative responses by > 95{\%}. The inhibitory activity was observed 24 h through day 7 postinfection. The infection of MO was associated with a sustained elevation of intracellular levels of cAMP and the release of arachidonic acid (AA) and its metabolite PGE2 (activator of adenylate cyclase) in culture supernatants. The AA release was incidentally associated with TNF-α production. Monoclonal antibodies to TNF-α and pentoxyphylline (inhibitor of TNF synthesis) inhibited both AA and PGE2 release. The release of AA required protein synthesis and occurred under conditions consistent with the expression of CMV immediate early genes. Treatment of MO cultures at time of infection with 100 μM indomethacin or 1 μg of TNF-α mAb abolished the CMV-induced T cell inhibitory activity of the supernatants by 100{\%}. These data suggest that TNF dependent release of AA and PGE2 contributes to CMV-induced immunosuppression.",
keywords = "Cytokines, Immunosuppression, PGE, TNF-α, Viruses",
author = "Nokta, {Mostafa A.} and Hassan, {Mahmound I.} and Kimberly Loesch and Pollard, {Richard B}",
year = "1996",
month = "6",
day = "1",
language = "English (US)",
volume = "97",
pages = "2635--2641",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "11",

}

TY - JOUR

T1 - Human cytomegalovirus-induced immunosuppression

T2 - Relationship to tumor necrosis factor-dependent release of arachidonic acid and prostaglandin E2 in human monocytes

AU - Nokta, Mostafa A.

AU - Hassan, Mahmound I.

AU - Loesch, Kimberly

AU - Pollard, Richard B

PY - 1996/6/1

Y1 - 1996/6/1

N2 - Cytomegalovirus (CMV) has been associated with immunesuppression. Previously CMV was reported to interfere with signal transduction pathways in T cells. In this report the mechanisms underlying CMV-mediated immunosuppression were examined. Supernatants of CMV (Strains C-87, AD-169)-infected primary human monocyte (MO) cultures inhibited mitogenic T cell proliferative responses by > 95%. The inhibitory activity was observed 24 h through day 7 postinfection. The infection of MO was associated with a sustained elevation of intracellular levels of cAMP and the release of arachidonic acid (AA) and its metabolite PGE2 (activator of adenylate cyclase) in culture supernatants. The AA release was incidentally associated with TNF-α production. Monoclonal antibodies to TNF-α and pentoxyphylline (inhibitor of TNF synthesis) inhibited both AA and PGE2 release. The release of AA required protein synthesis and occurred under conditions consistent with the expression of CMV immediate early genes. Treatment of MO cultures at time of infection with 100 μM indomethacin or 1 μg of TNF-α mAb abolished the CMV-induced T cell inhibitory activity of the supernatants by 100%. These data suggest that TNF dependent release of AA and PGE2 contributes to CMV-induced immunosuppression.

AB - Cytomegalovirus (CMV) has been associated with immunesuppression. Previously CMV was reported to interfere with signal transduction pathways in T cells. In this report the mechanisms underlying CMV-mediated immunosuppression were examined. Supernatants of CMV (Strains C-87, AD-169)-infected primary human monocyte (MO) cultures inhibited mitogenic T cell proliferative responses by > 95%. The inhibitory activity was observed 24 h through day 7 postinfection. The infection of MO was associated with a sustained elevation of intracellular levels of cAMP and the release of arachidonic acid (AA) and its metabolite PGE2 (activator of adenylate cyclase) in culture supernatants. The AA release was incidentally associated with TNF-α production. Monoclonal antibodies to TNF-α and pentoxyphylline (inhibitor of TNF synthesis) inhibited both AA and PGE2 release. The release of AA required protein synthesis and occurred under conditions consistent with the expression of CMV immediate early genes. Treatment of MO cultures at time of infection with 100 μM indomethacin or 1 μg of TNF-α mAb abolished the CMV-induced T cell inhibitory activity of the supernatants by 100%. These data suggest that TNF dependent release of AA and PGE2 contributes to CMV-induced immunosuppression.

KW - Cytokines

KW - Immunosuppression

KW - PGE

KW - TNF-α

KW - Viruses

UR - http://www.scopus.com/inward/record.url?scp=0029938463&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029938463&partnerID=8YFLogxK

M3 - Article

VL - 97

SP - 2635

EP - 2641

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 11

ER -