Subset of CD4+ T cell clones expressing IL-3 receptor alpha-chains uses IL-3 as a cofactor in autocrine growth.
In this paper we demonstrate that IL-3 can act as a cofactor for the growth of some CD4+ T cells. This lymphokine synergized with IL-4 to induce both a unique set of protein tyrosine phosphorylations and the vigorous proliferation of the keyhole limpet hemocyanin-specific and I-Ab-restricted CD4+ Th0 cell clone, E6. In addition, neutralizing anti-IL-3 Abs specifically inhibited the growth of E6 T cells to Ag or anti-CD3 mAb stimulation. Finally, this T cell clone was shown to express both the IL-3R alpha-chain and an IL-3R beta-chain (AlC2A). An examination of other CD4+ T cell clones determined that one Th1 clone (A.E7), two Th0 clones (16B.2 and L9A.1), and one Th2 clone (D10.G4.1) were not influenced by the addition of rIL-3. However, proliferation of the Th2 clones CDC25 and CDC35 to CD3-stimulation was significantly enhanced by IL-3. The sensitivity of these latter two clones to IL-3 was also found to be associated with expression of IL-3R alpha-chains. Because E6 T cells are highly dependent on IL-4 for autocrine growth similar to Th2 cells, these results suggest that IL-3 may synergize with IL-4 to enhance the proliferation of a subset of IL-4-dependent CD4+ T cells, and the study indicates that IL-3R alpha-chain expression may be a specific marker of this CD4+ T cell subset.
Mueller
D L
DL
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455.
Chen
Z M
ZM
Schwartz
R H
RH
Gorman
D M
DM
Kennedy
M K
MK
D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004357:Drug Synergism; D007377:Interleukin-3 / Q000008:administration & dosage*; D015847:Interleukin-4 / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D019000:Phosphotyrosine; D016185:Receptors, Interleukin-3 / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D017252:CD3 Complex; D007377:Interleukin-3; D016185:Receptors, Interleukin-3; D015847:Interleukin-4; D019000:Phosphotyrosine; D014443:Tyrosine