Leukemia: Derived heat shock protein gp96-peptide complex contribution to T cell and dendritic cell activation

Abstract

The molecular chaperone, heat shock protein gp96 (HSP-gp96), has been shown to have roles in the synthesis, processing and transport of tumor antigens. Therefore, the capacity for HSP-gp96 to induce dendritic cells (DCs), thymus-dependent lymphocytes (T lymphocytes), natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) was investigated. Recombinant adenovirus (AD) containing HSP-gp96 (AD-gp96), as well as gp96-peptide complex from the human leukemia cell lines, K562, HL-60 and U937, was prepared. Purified gp96-peptide complex was found to stimulate the proliferation of T lymphocytes, increase the activity of NK cells and CTLs and induce the secretion of cytokines, compared with ADgp96. In the latter case, levels of IFN-γ and TNF-α were found to increase and levels of IL-12(P70) and IL- 10 decreased. In combination, these results indicated that the gp96-peptide complexes derived from the tumor cells contributed to the activation of lymphocytes and increase the presentation of tumor antigen. Furthermore, the chaperone function of gp96 promoted the maturation of DCs, enhanced the antigen presention function of DCs and induced the secretion of cytokines by DCs. Therefore, gp96-peptide complex derived from the tumor cells potentially represents an immunization therapy for the elimination of residual leukemia cells.

Key words: Leukemia, heat shock protein gp96, dendritic cells, cytotoxic T lymphocytes.