Whether SP thymocytes are stimulated in the presence of live or killed splenocytes, suggesting that the peptide-MHC complexes and other potential molecules present on the surface of splenocytes are sufficient for this process. Nonetheless, thymocytes are still incapable of producing producing TNF efficiently despite receiving LOUREIRIN-B optimal antigen presentation in the splenic environment. Contact with secondary lymphoid organs is vital for the completion of post-thymic maturation of developing SP thymocytes. RTEs that reach the periphery undergo phenotypic and functional maturation as they become resident in secondary lymphoid organs. Our findings indicate that the full competence for TNF production by naive T cells in the peripheral T cell pool is acquired gradually in a post-thymic maturation dependent manner. In mice, developing thymocytes emigrate and populate the periphery at the rate of 1�C2% of thymocytes per day Folinic acid calcium salt pentahydrate throughout the life. Therefore, at any given time in an adult immune system, the na? ive T cell pool is comprised of cells at various stages of post-thymic development, unlike neonates whose peripheral lymphoid organs are predominantly populated with RTEs. The post-thymic maturation status of T cells is a component that has been recently shown to influence T cell fate decisions at the time of antigen encounter. This study showed that RTEs produced fewer memory-precursor effector cells and more short-lived effector cells during the immune response to LCMV. Our data show that RTEs produce less TNF relative to MN T cells. Given the immunoregulatory functions of TNF, we speculate that the differential ability of TNF production linked to the post-thymic maturation status of antigen-specific na? ive T cells, may also contribute to influencing the fate of the responding T cells during the initial phase of activation. In conclusion, our findings indicate that the licensing of na? ive T cells for rapid TNF production is determined by their developmental state. It is an intrinsic property of the developing T cells that is acquired gradually, where functional maturation in secondary lymphoid organs drives developing na? ive T cells to eventually attain full competence to produce TNF efficiently during TCR stimulation. Androgens play a pivotal role in the control of spermatogenesis. Under a number of conditions they are even able to maintain fertility in the virtual absence of follicle stimulating hormone. Interestingly, most data indicate that the androgen receptor is not expressed in germ cells and that GC can develop normally in the absence of cell-autonomous AR expression. This indicates that androgens affect GC development indirectly by acting on somatic testicular cells. The development of animals with cell-selective knockouts of the AR in various somatic testicular cells points to the Sertoli cell as the key mediator of the effects of androgens in the control of spermatogenesis. In fact, mice with a selective knockout of the AR in SC develop a complete block in meiosis. Data on the consequences of a knockout of the AR in peritubular myoid cells are more controversial. Whereas original studies suggested that the latter knockout has only minor effects on GC development, more recent data indicate that those studies mainly targeted vascular smooth muscle cells and that more appropriate targeting of the AR in PTM causes major disturbances in spermatogenesis. Notably, secondary disturbances in SC and Leydig cells function appear to be one consequence of the ablation of the AR in PTM highlighting again the carefully balanced dialogue that exists between the different somatic cell types within the testis and the pivotal role the SC plays in orchestrating full, functional maturation of the GC cohort. Although our studies as well as those of others agree that AR-dependent modulation of SC function plays a critical regulatory role in supporting GC as they mature within the seminiferous epithelium, we are still some way from fully understanding the molecular mediators and pathways by which androgens orchestrate the relationship between SC and GC.