CD8 T cell responses to viral infections in sequence

Abstract

Our current understanding of virus-specific T cell responses has been shaped by model systems with mice, where naive animals are infected with a single viral pathogen. Paradigms derived from such models, however, may not always be applicable to a natural setting, where a host is exposed to numerous pathogens over its lifetime. Accumulating data in animal models and with some human diseases indicate that a host's prior history of infections can impact the specificity of future CD8 T cell responses, even to unrelated viruses. This can have both beneficial and detrimental consequences for the host, including altered clearance of virus, distinct forms of immunopathology, and substantial changes in the pool of memory T cells. Here we will describe the characteristics of CD8 T cells and the dynamics of their response to heterologous viral infections in sequence.

Figure 1

Response of both non‐cross‐reactive and cross‐reactive virus‐specific memory CD8 T cells to heterologous virus infections. This figure depicts the events occurring after a secondary infection of a virus‐immune mouse with a heterologous but cross‐reactive virus such as PV. Shown on the figure is the stability of memory CD8 T cells before re‐challenge, the virus‐induced lymphopenia, the peak of type 1 IFN, the peak of virus load, the expansion of T cells, the apoptotic decline, and the return to an immune state. It shows the loss of non‐cross‐reactive memory CD8 T cells and the maintenance of cross‐reactive memory.

Figure 2

CD8 T cells from LCMV‐immune mice are stimulated to divide following infection with homologous and heterologous viruses. Splenocytes from LCMV‐immune mice (Thy1.1) were labelled with CFSE and adoptively transferred into congenic naïve mice (Thy1.2). One day following transfer, recipient mice were left untreated, injected with poly(I:C), or infected with LCMV, PV, or VV. Six days later, splenocytes from recipient mice were stained with antibodies to CD8 and the congenic marker (Thy1.1) and then analysed by flow cytometry. The histograms showing the loss of CFSE were analysed by gating on cells positive for the donor marker and CD8. This figure was courtesy of S.K. Kim and based on previous studies ( Kim et al., 2002 ).

Figure 3

The immunodominance hierarchies of virus‐specific CD8 T cell responses are altered in mice that have been previously infected with a heterologous virus. The sections of the pie charts reflect the proportion of each epitope‐specific response relative to the T cell repertoire shown. The LCMV‐specific response is shown on the left and the PV‐specific response is shown on the right. The cross‐reactive T cells specific for the NP205 epitope are shown in red for both responses. The figure is based on previous studies ( Brehm et al., 2002 ).