Fas cross-linking mimics the inhibitory effect of anti-CD3 on IL-3-induced histamine and cytokine production by murine myeloid spleen cell precursors.
In the present study we investigated the effect of anti-CD3 stimulation on IL-3-induced histamine, IL-6, and IL-4 synthesis by murine hematopoietic precursor cells. These activities were strikingly decreased in splenocytes from mice that had received a single intravenous injection of 10 microg of anti-CD3 monoclonal antibody (mAb) 24 hours previously. A similar inhibition occurred after 24-hour in vitro stimulation of normal spleen cells with 1 microg/mL of anti-CD3 mAb. In both situations the inhibitory effect depended on T cell activation in that treatment with F(ab')2 fragments of anti-CD3 did not diminish secretion of histamine and cytokines. Cross-linking of Fas antigen on spleen cells mimicked the action of anti-CD3, provided that interferon (IFN)-gamma was present during the incubation period. Substantial amounts of this cytokine were detected in spleen cell supernatants, which were able to replace recombinant IFN-gamma during Fas receptor cross-linking. This effect was entirely mediated by IFN-gamma, as assessed by its neutralization in the presence of anti-IFN-gamma mAbs. In contrast to splenocytes, bone marrow cells responded normally to IL-3 after in vivo or in vitro stimulation with anti-CD3. They were also not affected by combined treatment with anti-Fas mAb and IFN-gamma. Together, our data support the notion that the decrease in IL-3-induced histamine and IL-6 production by splenocytes pretreated with anti-CD3 is mediated, at least in part, by Fas/FasL interactions, suggesting that the activity of extramedullary myeloid precursor cells can be modulated by molecules involved in apoptosis.
Université René Descartes-Paris V, Hôpital Necker, France.
A
A
Ben Amor
E
E
Schneider
A
A
Arnould
F
F
Machavoine
M
M
Dy
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001491:Basophils / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D003114:Colony-Forming Units Assay; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006632:Histamine / Q000096:biosynthesis* / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology; D007377:Interleukin-3 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016853:Muromonab-CD3 / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000378:metabolism; D019014:fas Receptor / Q000502:physiology*
D000911:Antibodies, Monoclonal; D007377:Interleukin-3; D015850:Interleukin-6; D016853:Muromonab-CD3; D012333:RNA, Messenger; D019014:fas Receptor; D015847:Interleukin-4; D006632:Histamine; D007371:Interferon-gamma