On T Cell Memory: Arguments for Antigen Dependence

Abstract

Memory is a hallmark of the immune system. Considerable progress has been made towards understanding B cell memory, but T cell memory remains poorly understood and its nature is controversial. There is good evidence that B cell memory is driven by antigen, but the antigen dependence of T cell memory is still being debated. For several years we have investigated the nature, duration and antigen dependence of different aspects of CD8+ T cell memory and this review will discuss our findings as well as how and why they differ from some other results. As others, we find that antigen, due to proliferation of antigen-specific T cell clones, induces a shift in the T cell repertoire which remains detectable for years as an elevated cytotoxic T cell precursor frequency (CTLp) in lymphoid organs. Also in the absence of antigen, in vitro assays for T cell memory which invariably isolate memory T cells from these lymphoid organs therefore remain positive. In contrast, immunity against reinfection with a pathogen requires more than just elevated numbers of CTLp in lymphoid organs. Since reinfection usually takes place via peripheral nonlymphoid tissue, these CTLp have to a) efficiently extravasate and patrol through such tissues, and b) be immediately able to exert effector function in case of reinfection. Both functions, require a certain level of activation which critically depends on T cell stimulation by persisting antigen.

Role of T cell help and endoplasmic reticulum targeting in protective CTL response against influenza virus

“…Obviously, these considerations are only relevant to the long-term consequences of priming by epitope-based immunization [31], including those utilizing helper-independent analogue CTL peptides [32]. Whether or not in our model high CTLp frequencies require persistent antigen [33] was not studied, but one cannot exclude that transgenic Ig may be stored on follicular DC as a long-term antigen depot [34].…”

A critical role for neutralizing-antibody-producing B cells, CD4+T cells, and interferons in persistent and acute infections of mice with lymphocytic choriomeningitis virus: Implications for adoptive immunotherapy of virus carriers

“…Initial virus control mediated by CTL is incomplete; LCMV persists at low levels in peripheral sites, from which it may periodically spread throughout the circulation. The obvious implication would be that virus persists after acute LCMV infection, thereby providing the basis for restimulation of protective, i.e., activated CTL memory (45,46). The following principles emerge for effective immunotherapy of LCMV infection.…”

Heat denaturation, a simple method to improve the immunotherapeutic potential of allergens

“…These adverse events frequently include a local reaction at the site of allergen injection, but also life-threatening systemic reactions such as asthma and anaphylaxis. This is why the administered allergen doses must be kept relatively low, which unfortunately favours Th2 immune responses in contrast to higher doses [3][4][5].Several strategies have been developed to tackle the problems of SIT, i.e. to reduce its side effects and to enhance its immunogenicity.…”