Activation-induced elimination of peripheral t cells by mcsf-derived macrophages (M08)

We have recently shown that human monocyte-derived Mfs exposed to macrophage colony-stimulating factor (MCSF) acquire the ability to induce apoptoais of T cells activated via T cell receptor (TOR) cross linking (J Immunol 156:523). We now employ a model using tranegenic mice to ask whether this novel phenomenon also occurs when T cells recognize antigen presented by MCSF-derived MøB. Mice were constructed on a H2Kk background which were either transgenic for a TCR recognizing H2Kb, or tranagenie for the H2Kb antigen itself. T cells from TCR-transgenic mice were cultured with MCSF-derived M#a expressing the target antigen. Under these conditions the T cells exited the resting state ae indicated by morphologic blastogenesisf but experienced uniform (>95%) cell cycle arrest near the Gl/S boundary. Arrested T cells progressively diad over the next 48-72 hrs without proceeding further through the cell cycle. MCSF-derived M$s that did not express the target antigen did not cause T cell death/ indicating that elimination of T cells required recognition of antigen. Furthermore/ in mixed co-culture experiments/ TCR-transgenic T cells were progressively eliminated while T cells that were not TCR-transgenic were spared, showing that Mip-mediated cell death was selective. Cell death waa not initiated by the fas/fas ligand system, since Møs from fas ligand-deficiant gId mice were fully suppreesive for T cells. We thus describe a novel mechanism whereby MCSF-derived Ms can selectively delete T cells which recognize antigens they present. Since tissue MøS normally present self antigens, we speculate that this mechanism may contribute to peripheral T cell tolerance.