title: Exposure of monocytes to heat shock does not increase class II expression but modulates antigen-dependent T cell responses.
abstract: Expression of heat shock (HS) proteins (HSP) increases after exposure to elevated temperatures or other types of injury, such as oxidative 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 degrees C for 20 min, allowed to recover for 2 h at 37 degrees 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 x 10(4)) and lymphocytes (1 x 10(5)) were co-cultured for 5 days in the presence of several antigens [diphtheria toxoid, tetanus toxoid or purified peptide derivative (PPD)] and labeled with 1 microCi [3H]thymidine for 16 h. Pre-exposure to HS (44 degrees C) significantly (P < 0.001) increased T cell responses to diphtheria toxoid, whereas the effect on the responses to other antigens (tetanus toxoid 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 enterotoxin B. The effect of HS was inhibited by actinomycin B and thus appeared dependent upon HSP synthesis. HSP-mediated increases in antigen processing may potentiate the ongoing immune response at inflammatory sites.
authors.affiliation: Allergy Unit, University Hospital, Geneva, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Mariéthoz
authors.forename: F
authors.initials: F
authors.lastname: Tacchini-Cottier
authors.forename: M
authors.initials: M
authors.lastname: Jacquier-Sarlin
authors.forename: F
authors.initials: F
authors.lastname: Sinclair
authors.forename: B S
authors.initials: BS
authors.lastname: Polla
mesh_terms: D017951:Antigen Presentation / Q000502:physiology*; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D004168:Diphtheria Toxoid / Q000276:immunology; D005434:Flow Cytometry; D006681:HLA-D Antigens / Q000096:biosynthesis*; D006358:Hot Temperature; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000276:immunology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology; D014373:Tuberculin / Q000276:immunology
chemical_list: D004168:Diphtheria Toxoid; D006681:HLA-D Antigens; D010835:Phytohemagglutinins; D018089:Superantigens; D013745:Tetanus Toxoid; D014373:Tuberculin; D003609:Dactinomycin