The Role of Accessory Cells in the Induction of Receptor-Mediated Human T Cell Growth.

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The present study was performed to made clear at molecular level the functions of accessory cells (AC) mediated by soluble factors released from AC and by cell-surface interaction between AC and T cells which are required for the induction of receptor-mediated human T cell proliferation.To dissect the AC functions into factor-mediated and cell contact-mediated functions, the AC-depleted peripheral blood (PB)-T cells were stimulated with anti-CD3-antibody coated on latex beads in a culture with or without macrophagederived soluble factors and paraformaldehyde (PFA)-fixed macrophages (f-Mo) and the T cell proliferation was examined. Major findings obtained in this study are summarized as follows.1) Both the factor-mediated and cell-contact-mediated accessory functions are required for the induction of the T cell proliferation.2) The soluble factors required were found to be IL-1 and IL-6. Both of these factors are indispensable because addition of either one of recombinant IL-1beta or IL … More -6 alone did not induce T cell proliferation, and the activity of Monoculture supernatant were diminished by adding either one of the neutralizing antibodies to IL-1beta or IL-6.3) A significant discovery in this study is that, before PFA-fixation, the macrophages had to be cultured with Con A-stimulated PB-mononuclear cells or interferon-gamma (IFN-gamma) to induce T cell proliferation. These results indicate that the expression of a certain cell-surface molecule (s) is induced by T cell-derived lymphokine (IFN-gamma) and this molecule is essential for the AC-T cell interaction.4) For AC-T cell interaction, inhibition studies with monoclinal antibodies (mAb) showed that interaction through LFA-1 and ICAM-1 is essential. In addition, a 200 Kd pan-leukocyte antigen was also shown to contribute significantly. This molecule is recognized by a mAd KW-23, raised in this study and appears to be a novel cell-interaction molecule.Thus our study demonstrated the dynamic bi-directional interaction between Mo and T cells. We proposed that, during the interaction, at least one of the necessary cell-interaction molecule is induced by IFN-gamma released from T cells. The Mo-T cell-interaction and soluble factors (IL-1 and IL-6) released from Mo induce IL-2 production and T cell proliferation. Less