These studies show that thymocytes are susceptible to infection with all strains of MeV tested. Immature CD4+CD8+ DP cells were most susceptible and susceptibility correlated with high expression of CD150 by this population of cells. DP thymocytes were more efficiently infected with WT strains of MeV than a vaccine strain. Thymus organ cultures from older children were often resistant to MeV infection and in one child this was associated with production of IFN-gamma within the culture.
The thymus is a target organ for MeV infection 
, but the cells infected by MeV have not been well characterized. Thymic epithelial cells are susceptible to MeV infection in vitro
and in human thymus/liver implants in SCID-hu mice 
. Human autopsy studies have shown immunocytochemical staining for MeV in Hassell’s corpuscles formed from epithelial cells in the medulla 
and in Warthin-Finkeldey giant cells formed from T cells in the cortex 
, suggesting that both populations may be involved in natural infection. Mice transgenic for human MeV receptors have provided a mixed picture of thymus cell susceptibility. Transgenic mice expressing human CD46 show virus replication in the thymus primarily in macrophages and dendritic cells 
, while MeV infection in the thymus of newborn transgenic mice expressing human CD150 is found in DP and CD4−
double negative cells 
. Stat-1−/− transgenic mice expressing the human CD150 gene also showed MeV RNA in the thymus 
, while IFNAR−/− mice with a knock-in chimeric human CD150 gene showed no infection in the thymus 
Our results demonstrate the susceptibility of DP human thymocytes to infection. DP cells are found primarily in the thymic cortex where they interact with morphogen-producing epithelial cells 
that are also susceptible to infection 
. The studies further suggest that CD150 plays an important role in MeV infection of DP thymocytes. This is consistent with the known distribution of human CD150 on DP thymocytes, as well as activated B and T lymphocytes and monocytes 
. However, receptor binding may not be the only factor dictating susceptibility to infection. CD4+
SP cells bound Edm B at comparable levels to immature DP cells, but were substantially less likely to express viral proteins. Because immature DP thymocytes are the most actively proliferating cells in TOC 
and MeV replicates more efficiently in mitogen-stimulated lymphocytes 
, proliferation status of DP cells may also enhance viral replication.
Some TOCs were resistant to MeV infection suggesting inhibition of virus replication that was correlated with the age of the child. We do not have measles vaccination histories for these children but presume that children over the age of 2 years would have received the live virus vaccine sometime between 12 and 15 months of age and be MeV-immune. Although the thymus is a primary lymphoid organ, antigen-specific memory T cells can re-enter the thymus where they are detected in the medulla 
. Lack of MeV replication after infection of TOC from older children may reflect the presence and activation of MeV-specific memory T cells resulting in suppression of MeV replication. IFN-gamma, detected in the culture of one older child, exerts an antiviral effect on epithelial, endothelial and astroglial cell lines, but not in B lymphoblastoid cell lines through induction of indoleamine 2,3-dioxygenase and perhaps other mediators that protect against MeV infection 
. TOCs from very young infants (<1 month) were also less susceptible than TOCs from children between 5 and 15 months, possibly due to high levels of residual maternal antibody 
. Identification of the actual mechanism of age-dependent protection from MeV infection in TOCs will require further investigation of larger numbers of children.
The importance of thymus infection for MeV-induced immunosuppression and predisposition to autoimmune disease is unclear. During measles there is lymphopenia, but this is transient and changes in the proportions of CD4+
T cells in circulation are modest 
. Maintenance of naïve T lymphocytes in circulation is dependent on continued production by the thymus. Changes in production of naïve T cells can be measured by quantifying T cell receptor rearrangement excision circles in the T cell population. During measles there is no deficit in production of CD4+
SP thymic emigrants, suggesting that a decrease in thymic output is not the cause of lymphopenia or depressed cellular immunity 
. However, infection may allow thymocyte release prior to negative selection 
and have long-term effects on the T cell repertoire through depletion of immature DP thymocytes.