IMMUNOACTIVE PRODUCTS OF PLACENTA .4. INDUCTION OF TRANSIENT MURINE T-CELL ANERGY BY A LOW-MOLECULAR-WEIGHT COMPOUND OBTAINED FROM SUPERNATANTS OF HUMAN PLACENTAL CULTURES

A low-molecular-weight material present in human placental supernatant (lymphocyte proliferation inhibiting factor, LPIF, or filtrate) can i nduce tolerance/hyporesponsiveness in vivo. We already knew from previ ous experiments that this material acted only on preactivated or malig nant T cells, and even the malignant cells could be rescued from its a ction if cells were washed quickly after contact. To understand the me chanisms of its action, we have set up systems of specific stimulation . The material inhibits anti-V beta-specific stimulation. In a mixed l ymphocyte reaction if responder cell populations from a first MLR perf ormed in the presence of LPIF are harvested, extensively washed to dis card suppressor molecules, and restimulated by related or third-party lymphocytes in an H-2-incompatible combination, the response to a thir d-party stimulator (a primary one) is unaffected by prior exposure to the material, which nevertheless renders the population unresponsive t o restimulation by the original MHC-stimulating haplotype. Cells trigg ered by anti-V beta 6 antibodies in the presence of LPIF are unable to undergo restimulation by the very same anti-V beta 6 MoAb, while they conserve their capacity to proliferate in a primary fashion in respon se to the unrelated anti-V beta 8 MoAb. When analyzed by FACS using an ti-V beta FITC-conjugated MoAbs, cells that are unresponsive or blocke d in their proliferation by the action of the filtrate after anti-V be ta stimulation are still live and unexpectedly transiently hyperexpres s the TcR. These findings confirm the requirement for T cell stimulati on for suppression to be enacted and demonstrate that such is exerted by anergy rather than by clonal deletion, at least in vitro. (C) 1997 Academic Press.