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 language | English (US) |
|---|---|
| Pages (from-to) | 2635-2641 |
| Number of pages | 7 |
| Journal | Journal of Clinical Investigation |
| Volume | 97 |
| Issue number | 11 |
| State | Published - Jun 1 1996 |
| Externally published | Yes |
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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 journal › Article
}
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 -