Evidence for the existence of IL-4 and IFN gamma secreting cells in the T cell repertoire of naive mice.
The kinetics with which IgE responses develop in vivo following immunization of experimental animals indirectly support the existence of IL-4-secreting T cells as a normal component of the T cell repertoire. At the same time, studies of IL-4-secreting cell frequencies directly ex vivo have argued that T cells with the potential to become IL-4 secretors exist in vivo, in the form of precursors requiring stimulation and 4-12 days of culture as well as restimulation with mitogen or Ag before they become detectable as lymphokine-secreting cells. We demonstrate here that intravenous administration of low doses of anti-CD3 mAb 145-2C11 results in IL-4 production within 60 min of stimulation as demonstrated by Northern analysis of mRNA and a sensitive, selective bioassay (CT.4S cell proliferation) of biologically active IL-4 protein. Production of IL-4 is paralleled by IFN gamma synthesis, displaying similar kinetics. These findings, consistent with the presence of mature cells capable of IL-4 and IFN gamma synthesis in the T cell repertoire of naive mice, are supported by the observation that stimulation of spleen cells from naive mice with anti-CD3 mAb in vitro for 12 h also results in strong IL-4 and IFN gamma mRNA and protein synthesis. The data support and extend those obtained through analysis of cytokine mRNA synthesis alone, thereby providing evidence that "fresh" T cells are indeed capable of producing IL-4 directly ex vivo and are consistent with the existence of IL-4-secreting cells as a normal component of the T cell repertoire of naive mice.
Wang
H
H
MRC Group for Allergy Research, University of Manitoba, Winnipeg, Canada.
Mohapatra
S S
SS
HayGlass
K T
KT
D000818:Animals; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015870:Gene Expression; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4; D007371:Interferon-gamma