An anti-DEC-205 monoclonal antibody stimulates binding of thymocytes to rat thymic dendritic cells and promotes apoptosis of thymocytes.

DEC-205, a transmembrane receptor responsible for cross-presentation of apoptotic cell-derived antigens, is expressed by cortical thymic epithelial cells (TEC) and thymic dendritic cells (TDC) in humans and mice, but its function in T-cell development is still unclear. In this work we have studied for the first time the expression of DEC-205 in the rat thymus by HD83 monoclonal antibody (mAb) and immunohistochemistry, as well as the ability of this mAb to modulate thymocyte - TDC interactions in vitro. We showed the positivity of cortical TEC in situ, including thymic nurse cells (TNC) in suspension, and TDC, whereas subcapsular, perivascular and medullary TEC were negative. All examined DEC-205 positive and DEC-205 negative structures were MHC class II positive. HD83 mAb increased apoptosis of thymocytes in co-culture with TDC in vitro and the process was associated with increased binding of thymocytes to TDC in a rosette form. Since negative selection of thymocytes by clonal deletion (apoptosis) was mediated predominantly by TDC, our results suggest the possible indirect effect of the DEC-205 molecule in these mechanisms.

Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats

The role of gonadal hormones in induction and, particularly, maintenance/progression of rat thymic involution, which normally starts around puberty, was reassessed by examining the effects of peripubertal orchidectomy on thymic weight and morphometric parameters at different times up to the age of 10 months. Up to 6 months post-castration both thymic weight and cellularity in orchidectomized (Cx) rats were greater than in age-matched control rats, sham Cx (Sx). The increase in thymic cellularity reflected an increase in thymocyte proliferation rate (the proportion of proliferating cells was 18.6 ± 0.7 percent in 2-month-old Cx (N = 5) vs 13.4 ± 0.3 percent (N = 5) in age-matched Sx rats) followed by reduced sensitivity to apoptotic signals (apoptotic thymocytes were 9.8 ± 0.9 percent in 2-month-old Cx (N = 5) vs 15.5 ± 0.3 percent (N = 5) age-matched Sx rats). However, 9 months post-orchidectomy, neither thymic weight and cellularity nor any of the morphometric parameters analyzed differed between Cx and control rats. The reduction of thymic cellularity in Cx rats to control values may be related to increased sensitivity of their thymocytes to apoptotic signals in culture (72.6 ± 1.2 percent in 10-month-old vs 9.8 ± 0.9 percent in 2-month-old Cx rats) followed by reduced responsiveness to proliferative stimuli (14.1 ± 0.2 percent in 10-month-old vs 18.6 ± 0.7 percent in 2-month-old Cx rats). Thus, the study indicates that the effects of peripubertal orchidectomy on thymic weight and cellularity, as well as on the main morphometric indices, are long-lasting but not permanent, i.e., that removal of the testes can only postpone but not prevent age-related organ atrophy and consequently functional deterioration of the immune system.