B7/CD28-dependent IL-5 production by human resting T cells is inhibited by IL-10.
We analyzed the effects of rIL-10 on IL-5 production by human resting T cells isolated from peripheral blood. Resting T cells of healthy individuals required activation for 48 h with either anti-CD3 mAb cross-linked on B7/CD32-transfected mouse fibroblasts or PMA in conjunction with anti-CD28 mAb for optimal IL-5 secretion. In each condition, IL-5 secretion measured by ELISA was inhibited in a dose-dependent manner by rIL-10, whereas IFN-gamma production was not suppressed. The inhibitory effect of rIL-10 on IL-5 synthesis induced by PMA and anti-CD28 mAb was also observed at the mRNA level. In contrast with its action on T cells costimulated by B7/CD28 signaling, rIL-10 did not block IL-5 secretion in response to PMA and A23187 calcium ionophore. The inhibition of IL-5 production by rIL-10 was not due to IL-2 deprivation because it was not modified by the addition of exogenous rIL-2. Moreover, cyclosporin A, which inhibited IL-2 more efficiently than rIL-10 in response to anti-CD3 mAb and B7/CD32 transfected fibroblasts, did not reduce and even enhanced IL-5 production. Finally, we analyzed the influence of endogenously produced IL-10 on IL-5 secretion by T cells stimulated by PMA and anti-CD28 mAb. Addition of a neutralizing anti-IL-10 mAb increased IL-5 release in this system, indicating that endogenous IL-10 controls IL-5 production. We conclude that both rIL-10 and endogenous IL-10 inhibit IL-5 production by T cells costimulated by B7/CD28 signaling.
Schandené
L
L
Department of Immunology, Erasmus Hospital, Brussels, Belgium.
Alonso-Vega
C
C
Willems
F
F
Gérard
C
C
Delvaux
A
A
Velu
T
T
Devos
R
R
de Boer
M
M
Goldman
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018122:B7-1 Antigen / Q000378:metabolism; D001483:Base Sequence; D018106:CD28 Antigens / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000235:genetics; D007399:Interphase; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D018106:CD28 Antigens; D017931:DNA Primers; D015848:Interleukin-5; D016753:Interleukin-10; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate