Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Selection of a competent T-cell repertoire is dependent on complex interactions between immature thymocytes and components of the thymic stroma. These events may be preserved in vitro by excising developing thymus rudiments and maintaining them under carefully controlled conditions in fetal thymus organ cultures (FTOC). Using this approach, we have shown that the ability of C57B1/6 thymi to sustain positive selection of mature CD4+CD8- cells is profoundly influenced by the day of gestation on which they are excised: while thymocytes from day 14 rudiments fail to progress beyond the CD4+CD8+ stage of the developmental pathway, day 15 and day 16 thymi support the differentiation of CD4+CD8- thymocytes. Importantly, day 16 thymocytes transferred to day 14 deoxyguanosine-treated rudiments are likewise arrested at the CD4+CD8+ stage, suggesting that the thymic microenvironment of day 14 rudiments, rather than the state of differentiation of the thymocytes they contain, is responsible for the block in positive selection. Our studies of the stromal elements of day 14 rudiments have, however, revealed no obvious deficiencies in the cell types represented, or their expression of class II major histocompatibility complex (MHC) determinants. Furthermore, we have been unable to circumvent the blockage in positive selection by the addition of certain cytokines expressed late during gestation. These results suggest that subtle changes occurring at day 15 of ontogeny render the thymic microenvironment capable of positive selection.


Journal article



Publication Date





292 - 298


Animals, CD4-Positive T-Lymphocytes, Flow Cytometry, Gestational Age, Granulocyte-Macrophage Colony-Stimulating Factor, Immunohistochemistry, Interleukin-1, Interleukin-2, Interleukin-3, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Organ Culture Techniques, Thymus Gland