Early Infection Termination Affects Number of CD8+ Memory T Cells and Protective Capacities in Listeria monocytogenes-Infected Mice upon Rechallenge

Abstract

Here, we reevaluate the effects of early termination of infection on primary T cell expansion, subsequent memory cell development, and protective immunity. Using a murine Listeria monocytogenes (LM) infection model, we found the primary expansions of both CD4+ and CD8+ T cells were affected even when ampicillin was given as late as 60 h postinfection (p.i.). Subsequent development of CD8+ memory T cells was also impaired, although to a lesser extent, and only mice that received ampicillin at 24 h p.i. revealed a significant decrease in memory CD8+ T cells. Upon rechallenge with 1 × 105 CFU of LM, all ampicillin-treated mice cleared LM as effectively, and they generated similar amounts of Ag-specific CD8+ T cells as with untreated mice. However, mice that received ampicillin at 24 h p.i. lost their protective abilities when rechallenged with 7.5 × 105 CFU of LM. Ampicillin treatment also revealed early down-regulation of B7.1 and B7.2, but not CD40, on dendritic cells 72 h p.i. Our results have several important implications: 1) they argue against the hypothesis that brief exposure of T cells to an Ag is sufficient for full-fledged primary T cell responses and subsequent memory T cell development in vivo; 2) they suggest the existence of a reservoir of memory T cells, more than the immune system can possibly expand during secondary infection; and 3) they suggest that protective capacity is correlated with the number of preexisting memory T cells and that secondary expanding T cells play a limited role, at least in murine LM infection.

Persistence of Transgene Expression Influences CD8+T-Cell Expansion and Maintenance following Immunization with Recombinant Adenovirus

“…Similar results were recently observed in a model of Listeria monocytogenes infection, where the primary CD8 ϩ T-cell response was attenuated by treatment with antibiotics 24 h after primary infection. Although comparable frequencies of antigen-specific CD8 ϩ T cells were measurable in untreated and treated mice following secondary infection, the antibiotic-treated mice displayed impaired protection (43). These data indicate that proliferative capacity may provide only a limited measure of functional protective immunity.…”

Differential Kinetics of Antigen Dependency of CD4+ and CD8+ T Cells

“…However, there is also data that CD8 + T cell expansion is correlated with the continued duration of TCR stimulation in the context of both infections and sterile vaccinations (13)(14)(15)(16)(17)(18)(19)(20)(21). The reason for this discrepancy is currently unclear and cannot be explained by differences of protocol, experimental systems or availability of help or inflammation.…”

Repeated Exposure to Trace Amounts of Woodchuck Hepadnavirus Induces Molecularly Evident Infection and Virus-Specific T Cell Response in the Absence of Serological Infection Markers and Hepatitis

“…Evidence obtained thus far suggests that the dose of antigen determines the strength (magnitude) and breadth (clonality) of the antigen-specific response (58,59). T cell responses induced following exposure to low doses of antigen are impaired, i.e., they are rather oligoclonal and fail to provide protection against subsequent challenge (60,61). Similarly, low or suboptimal costimulation of antigen-presenting cells (APCs) induces a tolerant phenotype in interacting T cells (62,63).…”