Molecular cloning of rat interleukin 4 cDNA and analysis of the cytokine repertoire of subsets of CD4+ T cells.
Rat peripheral CD4+ T cells may be subdivided into two functionally distinct subpopulations (OX-22highCD4+ and OX-22lowCD4+) on the basis of their reactivity with the monoclonal antibody MRCOX-22, which recognizes a restricted epitope on the leukocyte common antigen (LCA, CD45). Previous studies have demonstrated the increased activity of the OX-22highCD4+ subset in assays of cell-mediated reactivity, whereas the reciprocal OX-22lowCD4+ subset provides the majority of help for B cells in secondary antibody responses. Analyses of in vivo function have subsequently shown that the autoreactive activity associated with the OX-22highCD4+ subset can be inhibited through a suppressor activity within the OX-22lowCD4+ subset, indicating a further immunoregulatory role for these cells. Since the differential production of lymphokines such as interferon-gamma (IFN-gamma) and interleukin 4 (IL4) is believed to regulate alternative effector responses to a particular antigen, we have compared the lymphokine mRNA profiles of activated OX-22highCD4+ and OX-22lowCD4+ subsets using nucleic acid probes specific for rat IL 2, IFN-gamma and IL4, the latter of which has been isolated by a polymerase chain reaction cloning technique and its sequence is described. A higher frequency of cells expressed IL 2 mRNA in the OX-22high subset, in accordance with the relative levels of IL2 protein produced. In contrast, more IFN-gamma mRNA was detected in the OX-22lowCD4+ subset 24 h after mitogenic stimulation although these cells have consistently been shown to produce less IFN-gamma protein than the OX-22highCD4+ subset. This apparent paradox was resolved by the finding that the IFN-gamma mRNA levels in the OX-22lowCD4+ subset declined rapidly after 24 h while the levels continued to rise in the OX-22highCD4+ population such that at 48 h the relative levels were reversed. We have also demonstrated a higher level of IL4 mRNA expression within the OX-22lowCD4+ subset, which is undoubtedly involved in the increased B cell helper activity mediated by this subpopulation and may be responsible, in part, for their active suppression of cell-mediated immune responses.
McKnight
A J
AJ
MRC Cellular Immunology Unit, Sir William Dunn School of Pathology, University of Oxford, GB.
Barclay
A N
AN
Mason
D W
DW
D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000032:analysis*; D003001:Cloning, Molecular; D004247:DNA / Q000302:isolation & purification; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D007376:Interleukin-2 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015704:CD4 Antigens; D007376:Interleukin-2; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma; D004247:DNA