Spontaneous and prostatic steroid binding protein peptide-induced autoimmune prostatitis in the nonobese diabetic mouse.
Chronic nonbacterial prostatitis is a poorly defined syndrome of putative autoimmune origin. To further understand its pathogenesis, we have analyzed autoimmune prostatitis in the NOD mouse, a strain genetically prone to develop different organ-specific autoimmune diseases. Spontaneous development of autoimmune prostatitis in the NOD male, defined by lymphomonuclear cell infiltration in the prostate gland, is well-established by approximately 20 wk of age and is stably maintained afterward. Disease development is indistinguishable in NOD and NOR mice, but is markedly delayed in IFN-gamma-deficient NOD mice. A T cell response to the prostate-specific autoantigen prostatic steroid-binding protein (PSBP) can be detected in NOD males before development of prostate infiltration, indicating lack of tolerance to this self Ag. The intraprostatic inflammatory infiltrate is characterized by Th1-type CD4(+) T cells, which are able to transfer autoimmune prostatitis into NOD.SCID recipients. We characterize here experimental autoimmune prostatitis, detected by intraprostatic infiltrate and PSBP-specific T cell responses, induced in 6- to 8-wk-old NOD males by immunization with synthetic peptides corresponding to the C1 subunit of PSBP. Three PSBP peptides induce in NOD mice vigorous T and B cell responses, paralleled by a marked lymphomononuclear cell infiltration in the prostate. Two of these peptides, PSBP(21-40) and PSBP(61-80), correspond to immunodominant self epitopes naturally processed in NOD mice after immunization with PSBP, whereas peptide PSBP(91-111) represents a cryptic epitope. These model systems address pathogenetic mechanisms in autoimmune prostatitis and will facilitate testing and mechanistic analysis of therapeutic approaches in this condition.
Penna
Giuseppe
G
BioXell, Milan, Italy.
Amuchastegui
Susana
S
Cossetti
Chiara
C
Aquilano
Francesca
F
Mariani
Roberto
R
Giarratana
Nadia
N
De Carli
Elena
E
Fibbi
Benedetta
B
Adorini
Luciano
L
D000595:Amino Acid Sequence; D000727:Androgen-Binding Protein / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001324:Autoantigens / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D060789:Prostatein; D011472:Prostatitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017634:Self Tolerance / Q000276:immunology
D000727:Androgen-Binding Protein; D001324:Autoantigens; D010446:Peptide Fragments; D060789:Prostatein; C522726:prostatic steroid binding protein, mouse