Chemokine Guidance of Central Memory T Cells Is Critical for Antiviral Recall Responses in Lymph Nodes

Abstract

SUMMARY A defining feature of vertebrate immunity is the acquisition of immunological memory, which confers enhanced protection against pathogens by mechanisms that are incompletely understood. Here, we compared responses by virus-specific naive T cells (TN) and central memory T cells (TCM) to viral antigen challenge in lymph nodes (LNs). In steady-state LNs, both T cell subsets localized in the deep T cell area and interacted similarly with antigen-presenting dendritic cells. However, upon entry of lymph-borne virus, only TCM relocalized rapidly and efficiently toward the outermost LN regions in the medullary, interfollicular and subcapsular areas where viral infection was initially confined. This rapid peripheralization was coordinated by a cascade of cytokines and chemokines, particularly ligands for TCM-expressed CXCR3. Consequently, in vivo recall responses to viral infection by CXCR3-deficient TCM were markedly compromised, indicating that early antigen detection afforded by intranodal chemokine guidance of TCM is essential for efficient anti-viral memory.

In vivo imaging of CD8+T cell-mediated elimination of malaria liver stages

“…It will be interesting to determine whether a similar process is happening with Plasmodium-specific cells in the liver. Moreover, we do not know which GPCRs are required for further T-cell recruitment and cluster formation; interestingly, it has been demonstrated that both specific and nonspecific T cells are recruited to the site of influenza virus infection in the lungs via CCR5 (27), whereas in the lymph node, CXCL9-CXCR3 interactions have been shown to be critical for the clustering of antigen-specific effector CD8 + T cells around DCs in viral infections (11,28).…”

Imaging CD8+T cells during diverse viral infections

“…During the anamnestic T cell response to LCMV infection, Sung et al found LN-resident CD8 C memory T cells were first located within the LN T cell zone. Within 8 hours of infection, however, 90% of memory CD8 C T cells relocated to the periphery of the LN, where they facilely eliminated virusinfected cells (22). This peripheral positioning was dependent on expression of the chemokine receptor CXCR3.…”

“…Examining a third (and actual murine!) virus, lymphocytic choriomeningitis virus (LCMV), Sung et al visualized infected cells in both the LN SCS and medulla, but not in the node's interior, consistent with the exclusion of molecules larger than 70 kDa (22). Viral vaccines (eg.…”

CD27 costimulation contributes substantially to the expansion of functional memory CD8+T cells after peptide immunization

“…Compared with primary T cells, memory CD8 + T cells show an increased cell frequency, longevity, improved effector function, and increased responsiveness to lower Ag concentration [19][20][21]. Nonetheless, memory T cells remain dependent on DC for reactivation, reflecting an ongoing requirement for costimulation [22,23].…”

“…Once established, high expression of CD27 is a feature of cells with a T CM -like phenotype and greater capacity for mounting recall responses compared with CD27 lo cells [14,16]. In contrast, CD27 lo cells are associated with a terminally differentiated/senescent memory T-cell phenotype in both humans and mice [17,18].Compared with primary T cells, memory CD8 + T cells show an increased cell frequency, longevity, improved effector function, and increased responsiveness to lower Ag concentration [19][20][21]. Nonetheless, memory T cells remain dependent on DC for reactivation, reflecting an ongoing requirement for costimulation [22,23].…”