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Increased PGE 2 Production Mediates the In Vitro Inhibitory Effect of the Human Immunodeficiency Virus P24 Immunosuppressive Heptapeptide Ch7
Author(s) -
Giacomini,
Maria Teresa Giordani,
Di Modugno,
Chersi,
Luzzati
Publication year - 1998
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.1998.00389.x
Subject(s) - immune system , cytokine , biology , in vitro , antibody , immunology , antigen , epitope , immunosuppression , interferon , biochemistry
Previous work from our laboratory demonstrated that a synthetic heptapeptide (Ch7), corresponding to a conserved sequence of human immunodeficiency virus (HIV) core protein p24 (amino acids 232–238), was able to specifically abrogate antigen‐induced responses in cultures of normal human peripheral blood lymphocytes (PBL). Addition of recombinant human interferon‐γ (IFN‐γ) to Ch7‐suppressed cultures restored the capacity to mount an antigen‐specific antibody response, suggesting that a cytokine imbalance may be at the basis of the Ch7 immunosuppressive activity. In the present paper we show that the Ch7‐dependent in vitro immunosuppression was accompanied by a significant up‐regulation of prostaglandin E 2 (PGE 2 ) production and induction of interleukin‐10 (IL‐10)‐secreting cells. In the presence of the PGE 2 inhibitor indomethacin, IL‐10 up‐regulation was prevented and the induction of a specific antibody response was partially restored. PGE 2 is indeed an important regulator of immune responses with the ability to differentially affect cytokine production. Thus, our results demonstrate that the Ch7 immunosuppressive epitope may primarily act by up‐regulating PGE 2 production and, through this mediator, by causing a cytokine dysregulation, finally responsible for immune response suppression.