Studies on the interaction between macrophages and T suppressor cells

Abstract

In this thesis three approaches were undertaken to study the phenomenon of immunological suppression:;A panel of macrophage variants with different capacities to activate H-2{dollar}\sp{lcub}\rm d{rcub}{dollar} restricted T helper cells were analyzed for their ability to induce L-glutamic acid{dollar}\sp{lcub}50{rcub}{dollar}-L-tyrosine{dollar}\sp{lcub}50{rcub}{dollar}(GT) specific suppression using a placque forming cell assay. Some were demonstrated to activate GT-specific suppression; others had lost the ability to activate suppression. One of these, B26 was shown to be incapable of activating H-2{dollar}\sp{lcub}\rm d{rcub}{dollar} suppressor cells but capable of activating H-2{dollar}\sp{lcub}\rm k{rcub}{dollar} suppressor cells. B26 specific antibodies were generated that could block B26 induced suppression of H-2{dollar}\sp{lcub}\rm k{rcub}{dollar} cells. Because suppression maps to the E locus, the E{dollar}\sb{lcub}\alpha{rcub}{dollar} and E{dollar}\sb{lcub}\beta{rcub}{dollar} genes of B26 were sequenced and found to be unmutated from the parental sequence. B26 is, therefore, an in vitro analog of the B10.A(3R), B10.A(5R) paradigm in suppression.;T suppressor cells express I-J determinants on their surface and anti-I-J antibodies block induction of suppression both in vivo and in vitro. It is clear that T suppressor cells require an antigen presenting cell (APC) for activation but the molecules on APC interacting with I-J are unknown. We sought to identify these I-J interacting molecules (I-J-IM) by mimicking I-J with monoclonal anti-idiotypic antibodies to an anti-I-J antibody. We generated monoclonal antibodies that block suppression in a MHC and I-J restricted way and used them to approach the biochemical characterization of I-J-IM.;Finally, we analyzed monocytes stimulated with two different growth factors for their ability to activate suppression. Granulocyte-monocyte colony stimulating factor (GM-CSF) and macrophage colony stimulating factor (CSF-1) were used to mature monocytes from bone marrow stem cells. These cells were assayed for induction of GT-specific suppression. GM-CSF monocytes are 8-16 times more potent inducers of suppression than CSF-1 monocytes. Gamma-interferon restores the capacity of CSF-1 macrophages to induce suppression to the level of GM-CSF macrophages.