The molecular basis of granuloma formation in schistosomiasis: IV. T cell-derived suppressor-inducer and suppressor-effector factor reactivities are regulated by a TCR β chain analog

Abstract

In Schistosomiasis mansoni, granulomatous modulation is mediated by antigenically and genetically restricted T suppressor-inducer and suppressor-effector cells and the soluble factors which they produce. The T suppressor-inducer factor (TsiF) is produced by an L3T4 +, 14–30 + T cell. TsiF does not suppress directly, but induces the production of T-cell-derived suppressor-effector factor (TseF). TseF directly suppresses granuloma formation in vitro and in vivo. This study describes the molecular properties of TsiF. The factor is a nonimmunoglobulin heterodimer which can be separated into two component chains by dithiothreitol (DTT) reduction. The α chain imparts antigenic specificity and bears both the AgR and the epitope recognized by mAb 14–30 which characterizes T cells and factors of the Tsi phenotype. The β chain imparts genetic restriction and bears both the I-J phenotypic marker and a T-cell receptor for Ag (TCR) V β 8 determinant. These two chains can complement each other in vitro to reconstitute functional activity. The β chain also determines the functional activity of T cell-derived suppressor factor (TsF). A β chain, derived from TsiF, can complement the α chain derived from TsiF or TseF to reconstitute TsiF, but not TseF functional activity. Conversely the β chain of TseF can reconstitute only TseF activity. These findings suggest that TsiF bears structural homologies to the TCR borne by Tsi cells and that the β chain mediates the mode of functional interactions between TsFs and their target cells.