acase@tulane.edu / Recent thymic emigrants (RTEs) are the youngest subset of peripheral T cells, which are known to differ in how they functionally contribute to the naïve T cell pool. This distinctive cell population is known to contribute to the maintenance of T cell receptor diversity in the peripheral T cell pool, but their involvement in combating chronic bacterial infections, such as typhoid fever, has not been explored. In the present study, we hypothesized that RTEs are essential contributors to the CD4 T cell response during persistent Salmonella Typhimurium infection, which predominantly relies on helper T cell immunity to control bacteria. To test this hypothesis we performed thymectomy or sham surgical treatment on mice, either prior to or during, an established, chronic Salmonella infection and measured disease outcomes. We found that thymic output is crucial in the formation of protective immune responses during the establishment of a Salmonella infection, but appears to be dispensable once the Salmonella infection is established. We found that thymectomy prior to infection resulted in increased infection-associated mortality, increased bacterial burdens and increased numbers of antigen-specific CD4+ T cells. Furthermore, it appears that thymectomized mice may be impaired in their ability to produce effector cytokines at early time points of infection, compared to thymically intact mice. In contrast, when thymectomy was performed 30 days after the initiation of Salmonella infection, there were no observable differences in survival, bacterial burdens or antigen-specific CD4+ T cell numbers through out infection. To directly study the contribution of RTEs to the Salmonella immune response, we developed an adoptive transfer model where purified RTEs could be transferred to a congenically marked host immediately prior to Salmonella infection and their responses could be tracked throughout infection. We found that RTEs are capable of proliferating and upregulating maturation markers in response to antigen; comparable to other mature, naïve CD4+ T cells. Together, these results may imply a unique role for thymic output and or recent thymic emigrants in the formation of early immune responses against a chronic, enteric pathogen like Salmonella. However, once the pathogen has disseminated systemically, thymic function does not appear to play a vital role in protective immune response. / 1 / James Alan Goggins
| Identifer | oai:union.ndltd.org:TULANE/oai:http://digitallibrary.tulane.edu/:tulane_74456 |
| Date | January 2016 |
| Contributors | Goggins, James (author), McLachlan, James (Thesis advisor), School of Medicine Biomedical Sciences Graduate Program (Degree granting institution) |
| Publisher | Tulane University |
| Source Sets | Tulane University |
| Language | English |
| Detected Language | English |
| Type | Text |
| Format | electronic, 165 |
| Rights | No embargo, Copyright is in accordance with U.S. Copyright law. |
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