Modulation of Suppressor T-Cells by Streptococcal Pyrogenic Exotoxin

Abstract

The V-region gene repertoire which determines the qualitative nature of an organisms’ antibody response is encoded in the genome of the immunoglobulin forming cells (B-lymphocytes) of the organism. Other cells such as thymus derived lymphocytes (T-cells) and macrophages appear to regulate or control the antibody responses of B- lymphocytes to many immunogens including trinitrophenylated rabbit erythrocytes (TNP-RE). Recently, we have been attempting to understand how this regulation is mediated at the cellular level. We have devised a model based on the observation that a toxic protein (SPE) which is elaborated by many Group A streptococci is capable of deregulating T-cell dependent antibody responses in mice. An in vitro cellular complementation system allowed us to perform reconstruction experiments in order to define the functions of isolated subpopulations of mouse spleen immunocytes, which include B-cells and macrophages obtained from NFR/nu nu mice and T-cells obtained from their +/nu littermates. Since these subpopulations of immunocytes are all required in order to generate a complete anti-TNP PFC response in Marbrook-type spleen cell cultures, we were able to test and to localize the susceptible target of SPE within the T-cell population. Subfractionation of the T-cell population into functional distinct subpopulations followed by demonstration of the unique T-cell surface markers on the cells which bound SPE allowed us to delineate the deregulating locus of SPE to native regulatory T-cells or to a normal suppressor T-cell subset.