The recombinant 65-kD heat shock protein of Mycobacterium bovis Bacillus Calmette-Guerin/M. tuberculosis is a target molecule for CD4+ cytotoxic T lymphocytes that lyse human monocytes

Abstract

Since little is known about Tc cells in the human immune response to intracellular parasites, we have studied the role of Tc cells in response to M. bovis Bacillus Calmette-Guerin (BCG). Donors whose PBMC responded to BCG, purified protein derivative (PPD), and the recombinant 65-kD heat shock protein (HSP) of BCG generated BCG/PPD-specific CD4+ effector T lymphocytes that lysed PPD as well as recombinant 65-kD-pulsed monocytes. Nonpulsed or irrelevant antigen-pulsed target cells were lysed to a much lower but still significant extent. PPD-stimulated effector lymphocytes of a recombinant 65-kD nonresponder lysed PPD but not recombinant 65-kD-pulsed monocytes. Recombinant 65-kD-educated effector lymphocytes lysed both recombinant 65-kD- and PPD-pulsed monocytes. In addition, these effector cells efficiently lysed nonpulsed target cells. These results demonstrate that in recombinant 65-kD responders, the recombinant 65-kD HSP of BCG is an immunodominant target as well as a triggering molecule for BCG/PPD-specific CD4+ cytotoxic T cells that lyse autologous monocytes. The implications of these findings with respect to the role of the 65-kD HSP in autoimmunity are discussed.