Fuel and brake of memory T cell inflation

• Published in: Medical microbiology and immunology Vol. 208; no. 3-4; pp. 329 - 338
• Main Authors: Welten, Suzanne P. M., Baumann, Nicolas S., Oxenius, Annette
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2019; Springer Nature B.V
• Subjects: Activation; Antigens; Antigens, Viral - immunology; Bioaccumulation; Biomedical and Life Sciences; Biomedicine; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cytomegalovirus; Cytomegalovirus - growth & development; Cytomegalovirus - immunology; Cytomegalovirus Infections - immunology; Cytomegalovirus Infections - virology; Effector cells; Epitopes; Immunologic Memory; Immunological memory; Immunology; Infections; Inflation; Inoculum; Lymphocytes; Lymphocytes T; Medical Microbiology; Memory cells; Review; The Special Issue on Immunological Imprinting during Chronic Viral Infection; Tissues; Tumors; Vaccines; Vectors; Virology; Virus Activation; Virus Latency; Viruses; CD8 T cell; Cytomegalovirus infection; Memory inflation
• ISSN: 0300-8584; 1432-1831
• DOI: 10.1007/s00430-019-00587-9

Memory T cell inflation is a process in which a large number of effector memory T cells accumulates in peripheral tissues. This phenomenon is observed upon certain low level persistent virus infections, but it is most commonly described upon infection with the β-herpesvirus Cytomegalovirus. Due to the induction of this large pool of functional effector CD8 T cells in peripheral tissues, the interest in using CMV-based vaccine vectors for vaccination purposes is rising. However, the exact mechanisms of memory T cell inflation are not yet fully understood. It is clear that repetitive exposure to antigen is a key determinant for memory inflation, and therefore the viral inoculum dose and the subsequent number of viral reactivation events strongly impact on the magnitude of the inflationary T cell pool. In addition, the number of CMV-specific CD8 T cells that is able to sense these reactivation events affects the size of the inflationary T cell pool. In the following, we will discuss factors that either promote or limit T cell inflation from both the virus and host perspective. These factors mostly operate by influencing the amount of available antigen or by affecting the T cell pool that is able to respond to the antigen. Furthermore, we will discuss the recent use of CMV-based vaccines in pre-clinical experimental settings, where these vectors have shown promising results by inducing prolonged effector memory T cell responses to foreign-introduced epitopes and thereby provided protection from subsequent virus or tumour challenges.