The molecular basis of granuloma formation in schistosomiasis. IV. T cell-derived suppressor-inducer and suppressor-effector factor reactivities are regulated by a TCR beta chain analog.
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 alpha 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 beta chain imparts genetic restriction and bears both the I-J phenotypic marker and a T-cell receptor for Ag (TCR) V beta 8 determinant. These two chains can complement each other in vitro to reconstitute functional activity. The beta chain also determines the functional activity of T cell-derived suppressor factor (TsF). A beta chain, derived from TsiF, can complement the alpha chain derived from TsiF or TseF to reconstitute TsiF, but not TseF functional activity. Conversely the beta 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 beta chain mediates the mode of functional interactions between TsFs and their target cells.
Perrin
P J
PJ
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
Phillips
R J
RJ
Phillips
S M
SM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D000939:Epitopes; D006099:Granuloma / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007165:Immunosuppression Therapy; D051379:Mice; D008815:Mice, Inbred Strains; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000473:pathology; D013491:Suppressor Factors, Immunologic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013491:Suppressor Factors, Immunologic