T Cell and APC Dynamics In Situ Control the Outcome of Vaccination

Abstract

The factors controlling the progression of an immune response to generation of protective memory are poorly understood. We compared the in situ and ex vivo characteristics of CD8 T cells responding to different forms of the same immunogen. Immunization with live Listeria monocytogenes, irradiated L. monocytogenes (IRL), or heat-killed L. monocytogenes (HKL) induced rapid activation of CD8 T cells. However, only IRL and live L. monocytogenes inoculation induced sustained proliferation and supported memory development. Gene and protein expression analysis revealed that the three forms of immunization led to three distinct transcriptional and translational programs. Prior to cell division, CD8 T cell–dendritic cell clusters formed in the spleen after live L. monocytogenes and IRL but not after HKL immunization. Furthermore, HKL immunization induced rapid remodeling of splenic architecture, including loss of marginal zone macrophages, which resulted in impaired bacterial clearance. These results identify initial characteristics of a protective T cell response that have implications for the development of more effective vaccination strategies.

Tumor-infiltrating lymphocytes are dynamically desensitized to antigen but are maintained by homeostatic cytokine

“…4). In our previous imaging of early TIL interactions in the TME, we had exploited a reporter system consisting of a combination of the Cx3cr1gfp (27) and Cd11ccherry reporter alleles (28). Based on the relative expression of these reporters, monocyte-derived immature macrophages (TAM1) and mature macrophages (TAM2) can be distinguished from conventional dendritic cells (CD11b/CD103 DC; ref.…”

Splenic Priming of Virus-Specific CD8 T Cells following Influenza Virus Infection

“…36 to 72 h before cells begin to leave the secondary lymphoid organs (SLO) (30). As a consequence of these tight interactions mediated by TCR and enhanced adhesion molecule expression, responding T cells become "locked" in SLO during the early stage of the immune response (31)(32)(33)(34). These findings argue against the possibility of cells migrating from their original site of antigen encounter to other lymphoid organs during this early phase of antigen presentation.…”

“…Naive T cells recruited into the response throughout the course of the infection are likely to encounter decreasing levels of antigen and inflammation and will face increasing competition for antigen and resources as responding T cells expand. Effective T cell lineage differentiation likely requires multiple encounters with APCs for optimal expansion and differentiation (34,(61)(62)(63), which in turn may be affected by the time of recruitment. For example, the memory potential of CD4 T cells is inversely proportional to the number of cell divisions undertaken (59), while CD8 T cells that encounter antigen later after infection undergo fewer rounds of cell division but are preferentially recruited into the memory pool (60,64).…”

<i>Listeria monocytogenes</i> Inoculation Protects Mice against Blood-Stage <i>Plasmodium yoelii</i> Infection

“…Recent finding suggests that Lm killed by gamma-irradiation has similar effects as live bacteria in the induction of protective immunity (Datta et al 2006). Moreover, Khanna et al (2010) show that irradiated Lm (IRL) and live Lm inoculation can both induce sustained proliferation of CD8 + T cells and support memory development while HKLm fails to do so. These findings suggest that IRL may serve as a safe vaccine vector for recombinant antigens and it is worthy to further investigate the protective effect of IRL on malaria parasite infection.…”