Modulatory roles of RANTES in IL-4 production by human blood CD4(+)T cells.
An increase in serum IgE levels has been reported in several thrombotic cardiovascular diseases. Since such diseases are associated with the activation of platelets, we hypothesized that platelets are implicated in a mechanism leading to heightened IgE synthesis. To this end, we performed an in vitro investigation of the effects on IL-4 production caused by several bioactive substances potentially released from platelets. Human blood CD4(+)T cells from blood donors were stimulated with anti-CD3 antibody and costimulatory signals delivered via CD58 and CD80 in the presence or absence of IL-4. One of the following test substances was also included in the culture: platelet factor-4, beta-thromboglobulin, platelet-derived growth factor, serotonin, platelet activating factor, or RANTES. The cells were restimulated in the absence of IL-4 and test substances. Among the six substances, RANTES alone exhibited significant effects on IL-4 production. RANTES enhanced IL-4 production in the presence of IL-4, whereas it suppressed IL-4 production in the absence of IL-4. The enhancing effect of RANTES was positively correlated with plasma IgE levels in the donors. We concluded that RANTES may induce IgE synthesis by increasing IL-4 production in individuals predisposed to high IgE responses. Our observations indicate a link between platelets and immune phenomena associated with increased IgE responses.
Saito
S
S
First Department of Medicine, Hokkaido University, Sapporo, Japan.
Yamaguchi
E
E
Nakayama
H
H
Miyamoto
K
K
Kawakami
Y
Y
D000328:Adult; D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018968:CD58 Antigens / Q000378:metabolism; D018946:Chemokine CCL5 / Q000097:blood* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D051379:Mice; D010972:Platelet Activating Factor / Q000494:pharmacology; D010978:Platelet Factor 4 / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D001620:beta-Thromboglobulin / Q000494:pharmacology
D018122:B7-1 Antigen; D017252:CD3 Complex; D018968:CD58 Antigens; D018946:Chemokine CCL5; D010972:Platelet Activating Factor; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D001620:beta-Thromboglobulin; D015847:Interleukin-4; D012701:Serotonin; D010978:Platelet Factor 4; D007073:Immunoglobulin E; D007371:Interferon-gamma