Adaptive immunity to cytomegalovirus infection
Acute infection with the β-herpes virus cytomegalovirus (CMV) induces disseminated lytic replication which is controlled by the concerted action of various immune effector cells, followed by life-long latency. It is assumed that CMV sporadically undergoes reactivation events from latency that are rapidly controlled by adaptive immunity. Therefore, CMV infection is optimally suited to study CD8 T cell responses in the context of a latent/persistent viral infection. Humans and mice are natural hosts of CMV and both elicit a remarkably large CMV-specific memory CD8 T cell response which increases with time, a phenomenon referred to as "memory CD8 T cell inflation". The mechanisms leading to this "memory CD8 T cell inflation" are still poorly defined and our goal is to define its molecular and cellular mechanisms, to determine the reason(s) for the epitope selectivity of memory T cell inflation, to delineate the factors which set an upper limit to the expansion of inflating CD8 T cells, to reveal selection processes which operate during CD8 T cell inflation and to unravel the requirements for their tissue recruitment and tissue maintenance.
For MCMV-specific CD4 T cell responses we are aiming at understanding their differentiation and homing properties to particular tissues during acute and latent infection to delineate their protective capacity in glandular tissues such as the salivary gland, with a particular emphasis on the spatio-temporal localization and action of CMV-specific CD4 T cells.
Related publications:
Torti, N., S. M. Walton, T. Brocker, T. Rulicke, and A. Oxenius. 2011. Non-Hematopoietic Cells in Lymph Nodes Drive Memory CD8 T Cell Inflation during Murine Cytomegalovirus Infection. PLoS Pathog 7: e1002313. [external pageAbstract]
Torti, N., S. M. Walton, K. M. Murphy, and A. Oxenius. 2011. Batf3 transcription factor-dependent DC subsets in murine CMV infection: differential impact on T-cell priming and memory inflation. Eur J Immunol 41: 2612-2618. [external pageAbstract]
Walton, S. M., S. Mandaric, N. Torti, A. Zimmermann, H. Hengel, and A. Oxenius. 2011. Absence of cross-presenting cells in the salivary gland and viral immune evasion confine cytomegalovirus immune control to effector CD4 T cells. PLoS Pathog 7: e1002214. [external pageAbstract]
Walton, S. M., N. Torti, S. Mandaric, and A. Oxenius. 2011. T-cell help permits memory CD8(+) T-cell inflation during cytomegalovirus latency. Eur J Immunol 41: 2248-2259. [external pageAbstract]
Mandaric, S., S. M. Walton, T. Rulicke, K. Richter, M. J. Girard-Madoux, B. E. Clausen, A. Zurunic, M. Kamanaka, R. A. Flavell, S. Jonjic, and A. Oxenius. 2012. IL-10 Suppression of NK/DC Crosstalk Leads to Poor Priming of MCMV-Specific CD4 T Cells and Prolonged MCMV Persistence. PLoS Pathog 8: e1002846. [external pageAbstract]
Jeitziner, S. M., S. M. Walton, N. Torti, and A. Oxenius. 2013. Adoptive transfer of cytomegalovirus-specific effector CD4(+) T cells provides antiviral protection from murine CMV infection. Eur J Immunol 43: 2886-2895. [external pageAbstract]
Thom, J. T., S. M. Walton, N. Torti, and A. Oxenius. 2013. Salivary gland resident APCs are Flt3L- and CCR2-independent macrophage-like cells incapable of cross-presentation. Eur J Immunol. [external pageAbstract]
Thom, J. T., T. C. Weber, S. M. Walton, N. Torti, and A. Oxenius. 2015. The Salivary Gland Acts as a Sink for Tissue-Resident Memory CD8(+) T Cells, Facilitating Protection from Local Cytomegalovirus Infection. Cell Rep 13: 1125-1136. [external pageAbstract]
Klenerman, P., and A. Oxenius. 2016. T cell responses to cytomegalovirus. Nat Rev Immunol 16: 367-377. [external pageAbstract]
Thom, J. T., and A. Oxenius. 2016. Tissue-resident memory T cells in cytomegalovirus infection. Curr Opin Virol 16: 63-69. [external pageAbstract]
Baumann, N. S., N. Torti, S. P. M. Welten, I. Barnstorf, M. Borsa, K. Pallmer, J. D. Oduro, L. Cicin-Sain, K. Ikuta, B. Ludewig, and A. Oxenius. 2018. Tissue maintenance of CMV-specific inflationary memory T cells by IL-15. PLoS Pathog 14: e1006993. [external pageAbstract]
Welten, S. P. M., I. Sandu, N. S. Baumann, and A. Oxenius. 2018. Memory CD8 T cell inflation vs tissue-resident memory T cells: Same patrollers, same controllers? Immunol Rev 283: 161-175. [external pageAbstract]
Baumann, N. S., S. P. M. Welten, N. Torti, K. Pallmer, M. Borsa, I. Barnstorf, J. D. Oduro, L. Cicin-Sain, and A. Oxenius. 2019. Early primed KLRG1- CMV-specific T cells determine the size of the inflationary T cell pool. PLoS Pathog 15: e1007785. [external pageAbstract]
Welten, S. P. M., N. S. Baumann, and A. Oxenius. 2019. Fuel and brake of memory T cell inflation. Med Microbiol Immunol 208: 329-338. [external pageAbstract]