Functional and phenotypic characteristics of testicular macrophages in experimental autoimmune orchitis

C RIVAL; MS THEAS; MO SUESCUN; P JACOBO; V GUAZZONE; N VAN ROOIJEN; L LUSTIG

JOURNAL OF PATHOLOGY

JOHN WILEY & SONS LTD

Año: 2008 vol. 215 p. 108 - 117

0022-3417

Experimental autoimmune orchitis (EAO) is a model of organ-specific autoimmunity and testicular inflammation. EAO is characterized by an interstitial inflammatory mononuclear cell infiltration, damage of the seminiferous tubules and germ cell apoptosis. Here we studied the phenotype and functions of testicular macrophages during the development of EAO. By stereological analysis, we detected an increased number of resident (ED2+) and nonresident (ED1+) macrophages in the testicular interstitium of rats with orchitis. We showed that this increase was mainly due to monocyte recruitment. The in vivo administration of liposomes containing clodronate in rats undergoing EAO led to a reduction in the number of testicular macrophages, which correlated with a decreased incidence and severity of the testicular damage and suggests a pathogenic role of macrophages in EAO. By immunohistochemistry and flow cytometry we detected an increased number of testicular macrophages expressing MHC class II, CD80 and CD86 costimulatory molecules in rats with orchitis. Also, testicular macrophages from rats with EAO showed a higher production of IFN-gamma (ELISA). We conclude that testicular macrophages participate in EAO development, and the ED1+ macrophage subset is the main pathogenic subpopulation. They stimulate the immune response through the production of pro-inflammatory cytokines and antigen presentation and thus activation of T cells in the target organ.