Selective production of interleukin 3 (IL3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro by murine L3T4+ T cells: lack of spontaneous IL3 and GM-CSF production by Ly-2-/L3T4- lpr subset.
Murine spleen and lymph node L3T4+ T cells were found to spontaneously produce high levels of interleukin 3 (IL3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in cultures containing 10% fetal calf serum (FCS) in the absence of other stimulation. The IL3 and GM-CSF activities in culture supernatants peake between the fifth and seventh day of culture. The specificity of the bioassays was attested by the use of rabbit anti-IL3 and anti-GM-CSF antibodies, as well as by the detection of a maximal accumulation of IL3 and GM-CSF mRNA on the fourth day. In contrast, no significant activities of IL2, IL4 or interferon-gamma were detected in these culture supernatants. The markedly limited production of IL3 and GM-CSF in cultures performed in 1% autologous normal mouse serum and the inhibitory effect of anti-Ia or anti-L3T4 monoclonal antibody strongly suggest that the selective production of most, if not all IL3 and GM-CSF by L3T4+ T cells is a result of activation of L3T4+ T cells by fetal calf serum. All the strains of mice tested except athymic nude mice produced substantial amounts of IL3 and GM-CSF during the culture. This is in contrast to a previous report (Palacios, Eur. J. Immunol. 1984. 14: 599), indicating that only spleen cells of the MRL strain homozygous for the lpr gene spontaneously release IL3 in cultures. We found that spleen and lymph node cells from MRL/MpJ-lpr/lpr or C57BL/6J-lpr/lpr mice released, in fact, much less IL3 and GM-CSF in cultures. This was, however, due to the high proportion of the peculiar lpr Ly-2-/L3T4-T cells in spleen and lymph nodes, since after depletion of this lpr T cell subset, lymph node cells from C57BL/6J-lpr/lpr mice produced IL3 and GM-CSF at levels comparable to those in C57BL/6J-+/+ mice. These results further support the notion that the lpr Ly-2-/L3T4- T cell subset is immunologically nonfunctional and its accumulation dilutes functional L3T4+ T cells in mice bearing the lpr mutation.
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D000950:Antigens, Ly / Q000032:analysis; D015152:Blotting, Northern; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000096:biosynthesis*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000096:biosynthesis*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007377:Interleukin-3 / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4; D007378:Interleukins / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000145:classification / Q000502:physiology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D007377:Interleukin-3; D007378:Interleukins; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor