Exposure of monocytes to heat shock does not increase class II expression but modulates antigen-dependent T cell responses

Expression of heat shock (HS) proteins (HSP) increases after exposure to elevated temperatures or other types of injury, such as oxldative injury. Because of their function as ‘molecular chaperones', HSP are suggested to participate in antigen processing and presentation. We have previously reported that HS modulates antigen presentation in a human EBV-transformed B cell line. Here we investigated the effects of HS on MHC class II expression and on antigen processing and presentation by human monocytes. Monocytes were isolated from peripheral blood of normal human volunteers, purified by adherence, then exposed to temperatures ranging from 37 to 45°C for 20 min, allowed to recover for 2 h at 37°C and used for immunofluorescence or as antigen presenting cells in autologous and heterologous lymphocyte proliferation assays. No increase in class II expression was detected as assessed by flow cytometry. Monocytes (3 × 104) and lymphocytes (1 × 105) were co-cultured for 5 days in the presence of several antigens [diphtheria toxold, tetanus toxold or purified peptlde derivative (PPD)] and labeled with 1 μCI [3H]thymldlne for 16 h. Pre-exposure to HS (44°C) significantly (P < 0.001) increased T cell responses to diphtheria toxold, whereas the effect on the responses to other antigens (tetanus toxold or PPD) were not significant. HS did not increase heterologous T cell responses nor T cell proliferation induced by the non-processed superantigens such as staphylococcal enterotoxln B. The effect of HS was inhibited by actlnomycln B and thus appeared dependent upon HSP synthesis. HSP-mediated increases in antigen processing may potentiate the ongoing immune response at inflammatory site