First Author | Poston TB | Year | 2017 |
Journal | J Immunol | Volume | 199 |
Issue | 8 | Pages | 2845-2854 |
PubMed ID | 28855311 | Mgi Jnum | J:254762 |
Mgi Id | MGI:6103690 | Doi | 10.4049/jimmunol.1700914 |
Citation | Poston TB, et al. (2017) A Chlamydia-Specific TCR-Transgenic Mouse Demonstrates Th1 Polyfunctionality with Enhanced Effector Function. J Immunol 199(8):2845-2854 |
abstractText | Chlamydia is responsible for millions of new infections annually, and current efforts focus on understanding cellular immunity for targeted vaccine development. The Chlamydia-specific CD4 T cell response is characterized by the production of IFN-gamma, and polyfunctional Th1 responses are associated with enhanced protection. A major limitation in studying these responses is the paucity of tools available for detection, quantification, and characterization of polyfunctional Ag-specific T cells. We addressed this problem by developing a TCR-transgenic (Tg) mouse with CD4 T cells that respond to a common Ag in Chlamydia muridarum and Chlamydia trachomatis Using an adoptive-transfer approach, we show that naive Tg CD4 T cells become activated, proliferate, migrate to the infected tissue, and acquire a polyfunctional Th1 phenotype in infected mice. Polyfunctional Tg Th1 effectors demonstrated enhanced IFN-gamma production compared with polyclonal cells, protected immune-deficient mice against lethality, mediated bacterial clearance, and orchestrated an anamnestic response. Adoptive transfer of Chlamydia-specific CD4 TCR-Tg T cells with polyfunctional capacity offers a powerful approach for analysis of protective effector and memory responses against chlamydial infection and demonstrates that an effective monoclonal CD4 T cell response may successfully guide subunit vaccination strategies. |