IL-3 promotes production of IL-4 by splenic non-B, non-T cells in response to Fc receptor cross-linkage.
A spleen cell population that lacks CD3, CD4, CD8, Thy-1, B220, and class II major histocompatibility complex cell-surface markers (non-B, non-T cells) produces IL-4 when cultured in wells coated with IgE. Their production of IL-4 in response to plate-bound (PB)-IgE is strikingly enhanced by IL-3, and in the presence of IL-3, these cells also produce IL-4 in response to PB-IgG2a. The effect of IL-3 is not mimicked by IL-1, IL-2, IL-5, IL-6, IL-7, granulocyte-macrophage CSF (GM-CSF) or IFN-gamma. Non-B, non-T cells cultured with IL-3 for 12 h acquire the capacity to produce enhanced amounts of IL-4 in response to subsequent culture with PB-Ig even if IL-3 is omitted from the second culture. Irradiated cells also respond to IL-3 with enhanced capacity to produce IL-4 to PB-Ig, indicating that cell proliferation is not required for the effect of IL-3. The IL-3 effect can be obtained in vivo; treatment of mice with a total dose 90,000 U of synthetic IL-3 over a 3-day period results in the presence of splenic and peritoneal cavity non-B, non-T cells that produce enhanced amounts of IL-4 in response to PB-Ig. The FcR that mediates the response to PB-IgE appears to be Fc epsilon RI because cells can be sensitized with IgE anti-DNP mAb, washed, cultured for 15 h at 37 degrees C, washed again, and stimulated to produce IL-4 with 0.1 to 1 ng/ml of TNP10-OVA. IL-3 does not appear to mediate its function by increasing the number of Fc epsilon RI because it can exert its effect when cultured with non-B, non-T cells after they have been sensitized with IgE anti-DNP. However, IL-3 pretreatment does affect the signaling process in that non-B, non-T cells sensitized with IgE anti-DNP show strikingly reduced production of IL-4 to concentrations of TNP10-OVA of 100 ng/ml or more whereas cells pretreated with IL-3 show little or no diminution in IL-4 production at concentrations of TNP10-OVA up to 1 microgram/ml.
Le Gros
G
G
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Ben-Sasson
S Z
SZ
Conrad
D H
DH
Clark-Lewis
I
I
Finkelman
F D
FD
Plaut
M
M
Paul
W E
WE
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology; D001854:Bone Marrow Cells; D016207:Cytokines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007377:Interleukin-3 / Q000096:biosynthesis / Q000494:pharmacology*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008215:Lymphocytes, Null / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011940:Receptor Aggregation; D011961:Receptors, Fc / Q000502:physiology*; D017455:Receptors, IgE; D013154:Spleen / Q000166:cytology
D000944:Antigens, Differentiation, B-Lymphocyte; D016207:Cytokines; D007074:Immunoglobulin G; D007377:Interleukin-3; D011961:Receptors, Fc; D017455:Receptors, IgE; D015847:Interleukin-4; D007073:Immunoglobulin E