Virus‐specific CD8 T cells: activation, differentiation and memory formation

Abstract

Wiesel M, Walton S, Richter K, Oxenius A. Virus-specific CD8 T cells: activation, differentiation and memory formation. APMIS 2009; 117: 356-81. CD8 T cells are pivotal for the control of many intracellular pathogens, and besides their role in immediate control of infections, CD8 T cells have the capacity to differentiate into long-lived antigenindependent memory CD8 T cells, at least in situations of acute and resolved infections. The population of memory cells is heterogeneous with respect to their phenotype, their anatomical localization and their functional capacities in order to afford optimal protection against secondary infections. In the past years, it has become clear that multiple in vivo parameters are involved in shaping the composition of the memory CD8 T cell population, including antigen load, duration and strength of CD8 T cell stimulation, the level of inflammation, availability of CD4 T cell help and CD8 T cell precursor frequencies. With respect to the timing when CD8 T cells are committed to become memory cells, several models have been proposed. In contrast to acute, resolved infection, the continued in vivo exposure to high levels of antigen during persistent chronic viral infection precludes the development of long-lived antigen-independent memory CD8 T cells and might even result in severe dysfunction of virus-specific CD8 T cells.

Type I IFN Substitutes for T Cell Help during Viral Infections

“…This finding is in line with our previous results showing that CD4 + T cells are dispensable for the maintenance and functionality of memory CD8 + T cells upon VVG2 infection (10). Although there is a large body of literature on T cell help-dependent programming of proliferation-competent memory CD8 + T cells (38), our previous data, together with recent studies (39), suggest that differences in the experimental models/infections account for the different outcome; thus, it is important to assess the T cell help dependence of (memory) CD8 + T cell responses and the underlying mechanisms in relation to the particular experimental system used.…”

“…P14 transgenic mice expressing a TCR specific for the LCMV peptide gp [33][34][35][36][37][38][39][40][41] were previously described (21). P14 mice were crossed with IFNAR 2/2 mice to yield IFNAR-deficient P14 cells.…”

“…In particular, we raised the question whether differences in T cell help dependence relate to distinct patterns of innate/inflammatory responses induced by a particular viral infection. Therefore, we set up an experimental system using adoptive transfer of TCR transgenic CD8 + T cells with specificity for the LCMV gp [33][34][35][36][37][38][39][40][41] epitope (P14 cells) followed by infection with a recombinant VVexpressing the LCMV glycoprotein (VVG2). We have previously shown that, in this setup, optimal expansion of P14 cells depends on the presence of T cell help (10).…”

Antigen amount dictates CD8+T‐cell exhaustion during chronic viral infection irrespective of the type of antigen presenting cell

“…During highly replicative chronic viral infections such as HIV-1, hepatitis B or hepatitis C virus infection in humans, or lymphocytic choriomeningitis virus (LCMV) in mice, virus-specific CD8 + T cells initially expand and acquire effector functions early after infection but then gradually lose these functions [1][2][3][4][5][6][7][8] in a hierCorrespondence: Prof. Annette Oxenius e-mail: oxenius@micro.biol.ethz.ch archical manner: first the ability to produce IL-2 and to proliferate, then TNF-α secretion and last IFN-γ production become impaired [9][10][11][12]. This T-cell dysfunction, also termed CD8 + T-cell exhaustion, is well studied after infection of mice with a high dose of LCMV clone 13 or LCMV-Docile [13].…”

A new TLR2 agonist promotes cross-presentation by mouse and human antigen presenting cells

“…C T cells play a critical role in host defense against viral infection and certain cancers, 2 and thus the development of vaccines that elicit a robust CD8 C T cell response is an area of great interest. Subunit vaccines do not usually induce CD8…”