Staphylococcal Enterotoxin-Dependent Cell-Mediated Cytotoxicity

Abstract

The relationship between microorganisms and mammals is regulated by a complex interplay between pathogenic and protective mechanisms. The primary defense against bacteria is mainly constituted of mechanical barriers, such as intact epithelial membranes, and nonspecific immune mechanisms, for example granulocytes and macrophages. Bacteria generally cause disease when these barriers are overridden. It has recently become increasingly clear, however, that specific immune responses mediated by antigen-specific T and B lymphocytes are of critical importance as a physiological barrier capable of controlling the growth of invading bacteria. Patients with selective defects in specific immunity suffer from an increased susceptibility to bacteria, including those that are non-pathogenic in the normal host. Insight into the strategies employed by bacteria to evade immune recognition is accumulating. Several bacterial exoproteins have been reported to induce polyclonal activation of T or B lymphocytes with subsequent incapability to mount a specific immune response (Alouf 1986; Reimann et al. 1990). Moreover, excessive lymphokine production results in harmful effects on the integrity of tissues facilitating penetration of bacteria. Of particular interest is the description of bacterial products which interact with key elements of the specific immune system such as antibodies, MHC antigens, or T cell receptors. Staphylococcal and streptococcal cell wall proteins A and G have been shown to bind in a specific manner to immunoglobulins, and Branhamella catarrhalis and Haemophilus influenza interact with IgD on the surface of B lymphocytes (Boyle 1990). Recently, staphylococcal enterotoxins (SEs) and some related proteins have been shown to utilize MHC class II antigens as receptors on mammalian cells (Fischer et al. 1989; Fraser 1989; Mollick et al. 1989). The complexes, made up of toxin and MHC protein stimulate large numbers of T cells (White et al. 1989), and the subsequent excessive production of lymphokines may at least partly be responsible for their toxicity (Marrack et al. 1990). In the following we will describe a more subtle result of this interaction, the staphylococcal enterotoxin-dependent cellular cytotoxicity (SDCC) reaction, a possible mechanism for certain bacteria to evade specific immune recognition.