Immune modulation with high-dose heat-shock protein gp96: therapy of murine autoimmune diabetes and encephalomyelitis.
Immunization with heat-shock protein (HSP) gp96 elicits protective immunity to the cancer or virus-infected cells from which it is derived. Low doses of gp96 generate immunity, while doses 10 times the immunizing dose do not. We show here that injection of high doses of gp96 generates CD4(+) T cells that down-regulate a variety of ongoing immune responses. Immunization with high doses of gp96 prevents myelin basic protein- or proteolipid protein-induced autoimmune encephalomyelitis in SJL mice and the onset of diabetes in non-obese diabetic mice. The suppression of immune response can be adoptively transferred with CD4(+) cells and does not partition with the CD25 phenotype. The immunomodulatory properties of gp96 (and possibly other HSP) may be used for antigen-specific activation or suppression of cellular immune responses. The latter may form the basis for novel immunotherapies for autoimmune diseases.
Chandawarkar
Rajiv Y
RY
Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT 06030-1601, USA.
Wagh
Mihir S
MS
Kovalchin
Joseph T
JT
Srivastava
Pramod
P
D019264:Adoptive Transfer; D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D017690:Cell Transplantation; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology / Q000473:pathology; D006029:Glycosuria / Q000175:diagnosis; D007108:Immune Tolerance / Q000276:immunology; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use; D016233:Immunotherapy, Active / Q000379:methods*; D007328:Insulin / Q000032:analysis; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D016131:Lymphocyte Subsets / Q000637:transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D018991:Myelin Proteolipid Protein / Q000276:immunology / Q000494:pharmacology; D010179:Pancreas / Q000737:chemistry / Q000473:pathology; D010243:Paralysis / Q000175:diagnosis; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014611:Vaccination / Q000379:methods
D000951:Antigens, Neoplasm; D007155:Immunologic Factors; D007328:Insulin; D008070:Lipopolysaccharides; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D015375:Receptors, Interleukin-2; C435023:myelin proteolipid protein (139-151); C052646:sarcoma glycoprotein gp96 rejection antigens