T-cell Clonal Anergy

Abstract

Chemical fixation of splenic antigen-presenting cells (APC) with paraformaldehyde or 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (ECDI) destroys their ability to stimulate a proliferative response from interleukin-2 (IL-2)-producing T-cell clones (Jenkins and Schwartz 1987). In addition, exposure of the clones to antigen in the presence of the chemically fixed APC induces in them a hyporesponsive state to subsequent stimulation by normal APC and antigen (Fig. 1A). This induction of proliferative nonresponsiveness requires the correct allelic form of the major histocompatibility complex (MHC) class II molecule and the precise peptide recognized by the antigen receptor of the T-cell clone. These observations suggest that antigen-receptor occupancy is qualitatively normal and that the delivery of some other signal required for T-cell activation has been damaged by the fixation.