Proliferation of human CD4+45R+ and CD4+45R- T helper cells is promoted by both IL-2 and IL-4 while interferon-gamma production is restricted to IL-2 activated CD4+45R- T cells.
Recombinant IL-2 (rIL-2) and IL-4 (rIL-4) promote proliferation of human CD4+ T cells activated in the presence of PHA, TPA or OKT-3 monoclonal antibody (MAb), whereas the production of interferon-gamma (IFN) can be induced only by rIL-2. rIL-4 induced strong proliferative responses both in accessory cell independent assays and in the presence of autologous monocytes, but has failed to induce IFN production in any of these systems. The ability of rIL-2 to induce IFN production was strongly enhanced by the addition of monocytes, although a similar proliferative response was recorded in the absence or presence of monocytes. The MAb anti-Tac inhibited the proliferative response and the production of IFN by CD4+ T cells activated in the presence of rIL-2, whereas the proliferative response to rIL-4 was unaffected. CD4+45R+ and CD4+45R- T helper cell subsets proliferated in response to both IL-2 and IL-4. A kinetic analysis demonstrated that the production of IFN throughout a five day activation period was restricted to stimulation of CD4+45R- T cells with rIL-2. This report clearly demonstrates a dissociation of IFN production and T cell proliferation in man. While proliferation can be induced by both IL-2 and IL-4 in both the helper T cell subsets studied, IFN production was induced only in the CD4+45R- subsets and only in response to IL-2.
Dohlsten
M
M
Department of Tumor Immunology, Wallenberg Laboratory, University of Lund, Sweden.
Hedlund
G
G
Fischer
H
H
Sjögren
H O
HO
Carlsson
R
R
D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; D007376:Interleukin-2; D007378:Interleukins; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma