Evidence for T lymphocyte reactivity to the 65 kilodalton heat shock protein of mycobacterium in active Crohn's disease.

The role of mycobacterial heat shock proteins (Hsp) of the 65 kilodalton Hsp family as a possible factor governing cell-mediated immune responses, leading to chronic mucosal inflammation, was examined. Purified peripheral blood mononuclear cells (PBMC) from patients with CD and ulcerative colitis (UC), and from healthy and disease controls were stimulated in culture with a highly purified, recombinant 65 kilodalton Hsp (rHsp65) of M. bovis BCG for 5 d. Cultures were then pulsed with 3H-thymidine for 24 h and uptake determined by liquid scintillation. We found that PBMC from patients with active CD exhibited a significant proliferative response to the soluble rHsp65 as compared with normal controls. In contrast, the proliferative responses of PBMC from patients with inactive CD, inactive and active UC, pancreatitis and cecal carcinoma were found to be not different from controls. Purified T cells or non-T cells of PBMC in the absence of antigen-presenting cells from active CD patients exhibited a lack of proliferative responses to the rHsp65 stimulation in culture. The data indicate an aberrant sensitization of T cells to the 65 kilodalton mycobacterial Hsp in a specific type of IBD, and thus may provide an important clue for the etiopathogenesis of Crohn's disease.