Functional CD40 ligand expression on T lymphocytes in the absence of T cell receptor engagement: involvement in interleukin-2-induced interleukin-12 and interferon-gamma production.
Despite the fact that the great majority of T cells at the site of an inflammatory response are not antigen specific, the mechanisms leading to activation and recruitment of these bystander T cells are poorly understood. We previously reported that soluble (s)CD23 potentiated the interleukin (IL)-2-induced interferon (IFN)-gamma production by T cells co-cultured with autologous monocytes in the absence of T cell receptor (TCR) engagement. Our present data demonstrate that the IL-2-induced IFN-gamma secretion, in the presence but also in the absence of sCD23, is strictly IL-12 dependent, inasmuch as anti-IL-12 antibody abrogated both responses. Most interestingly, anti-CD40 ligand (CD40L) monoclonal antibody significantly inhibited IL-2-induced IL-12 as well as IFN-gamma production. These results suggest that CD40L was expressed on T cells in the absence of TCR engagement. Indeed, purified unstimulated T cells readily expressed CD40L. IL-2 and monocytes did not up-regulate CD40L on resting T cells. It is proposed that low levels of CD40L expression on non-antigen stimulated T cells are sufficient to signal through CD40 molecules on accessory cells and to induce IL-12 secretion, which in turn can synergize with IL-2 for the induction of IFN-gamma production, thus contributing to the inflammatory process.
Armant
M
M
University of Montreal, Louis-Charles Simard Research Center, Notre-Dame Hospital, Canada.
Armitage
R
R
Boiani
N
N
Delespesse
G
G
Sarfati
M
M
D000328:Adult; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand; D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000187:drug effects; D018664:Interleukin-12 / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000494:pharmacology*; D007399:Interphase / Q000276:immunology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D019013:CD40 Antigens; D007376:Interleukin-2; D008024:Ligands; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma