Neonatal castration affects intrathymic kinetics of T-cell differentiation and the spleen T-cell level

Abstract

To test putative interdependence in the ontogenesis of the hypothalamic–pituitary–gonadal and thymic–lymphatic axes, thymocyte differentiation and maturation was examined in neonatally castrated (Cx) adult rats. In the hypercellular thymi of Cx rats, the proportion of the least mature CD4−CD8−TCRαβ− triple negative (TN) thymocytes was reduced, while the proportions of all downstream double positive (DP) subsets (TCRαβ−, TCRαβlow and TCRαβhigh) were increased when compared with neonatally sham-castrated (Sx) adult rats. This suggested an accelerated thymocyte transition from the TN to DP TCRαβlow developmental stage accompanied by an increased positive/ reduced negative thymocyte selection. The increased thymocyte surface density of Thy-1, which is implicated in thymocyte hyposensitivity to negative selection, in Cx rats further supports the previous assumption. The finding that the proportions of both single positive (SP) TCRαβhigh thymocyte subsets were reduced, while their numbers were increased (CD4+CD8−) or unaltered (CD4−CD8+), coupled with results demonstrating an increased level of CD4−CD8+ cells without changes in that of CD4+8− cells in the spleen indicate: (i) accelerated differentiation and maturation of the positively selected DP TCRαβhigh thymocytes towards CD4−8+ TCRαβhigh cells followed by increased emigration of the mature cells and (ii) decelerated differentiation and maturation towards CD4+8−TCRαβhigh cells in Cx rats. Furthermore, the unaltered proportion of intrathymically developing CD4+CD25+Foxp3+ regulatory cells in Cx rats, in light of putative hyposensitivity of thymocytes to negative selection suggesting reduced elimination of autoreactive cells, may provide a firm basis for understanding the reasons behind increased susceptibility of Cx rats to autoimmune disease induction.