Mechanisms of suppression of cytotoxic T-cell responses in murine lymphocytic choriomeningitis virus infection.

Abstract

The cytotoxic T[thymus-derived]-cell response to lymphocytic choriomeningitis (LCM) virus infection was suppressed in vitro or in vivo by addition of a high level of syngeneic virus-infected cells or syngeneic cells from congenital LCM virus carriers to the environment of the responding cells. This effect was not duplicated by formaldehyde-fixed carrier cells, nor could it be accounted for by "cold" target competition by carrier cells at the level of the cytotoxicity assay. Suppression was produced in vivo by water-lysed, ultrasonically treated carrier cell suspensions, or by a large dose of LCM virus equivalent to that contained in the carrier cells. A high level of infectious virus was a common factor in all observed examples of suppression. The following hypothesis, a form of forbidden clone deletion, was proposed to account for virus-specific cytotoxic T-cell tolerance in LCM virus congenital carriers or in high dose suppression. A high level of virus in lymphoid tissues, while not cytopathic per se, may result in infection of all or most T cells; this may lead to deletion either via "suicide" of individual, infected, cytotoxic T cells with receptors specific for virus-induced antigenic patterns on their own surface membranes, or by mutual lysis of 2 adjacent T cells.