Roles of heat shock proteins and gamma delta T cells in inflammation

Abstract

Elimination of activated inflammatory cells that infiltrate and damage host organs can reduce morbidity and mortality. A better understanding of the mechanisms by which these processes occur may lead to new approaches to prevent tissue damage. The lungs, gastrointestinal tract, and skin are particularly prone to infection and collateral damage by inflammatory cells. Specialized lymphocytes protect these organs from collateral tissue damage by eliminating neutrophils and macrophages from inflamed tissues. These lymphocytes recognize signals produced by inflammatory cells. One such signal is heat shock protein (Hsp) expressed on the cell surface of inflamed phagocytes. Mammalian Hsp molecules closely resemble their microbial equivalents, and therefore phagocytes decorated with these molecules are recognized as target cells. T lymphocytes bearing the gammadelta T cell receptor (TCR) elicit cytotoxic activity toward macrophages and neutrophils that express Hsp60 and Hsp70, respectively, protecting host organs from collateral tissue damage by phagocytes.

Figure 1.

Schematic depiction of heat shock protein (Hsp)70-mediated killing of polymorphonuclear neutrophils (PMN) by γδT lymphocytes. Under normal conditions Hsp70 molecules of PMN are located in the cytoplasm, where Hsp70 is not recognized by γδT cells with Hsp70-specific T cell receptors. Under stress conditions (e.g., during inflammation), PMN express increased levels of Hsp70 molecules that translocate to the cell membrane, where they are recognized by Hsp70-specific γδT cells, serving these cells as markers that signal the elimination of the PMN bearing Hsp70.