Local inflammatory chemokines support the chronic activation of naïve influenza-specific CD8 T cells during the recovery from influenza infection (49.4)

Abstract

Abstract We previously found processed peptide antigens in the draining lymph nodes of the respiratory tract two months after primary influenza infection. These antigens were presented to naïve (but not central memory) CD8 T cells by CD11b+ DC. Many partially-activated F5 cells remained clustered in the paracortex of the MLN during late antigen presentation. Further studies show that the MLN remains enlarged >30dpi and contains larger numbers of CD11b+ DCs than resting LNs but the DC are not phenotypically mature. Consistently, RT-qPCR analysis shows very small quantities of cytokines in the lungs and DLNs during antigen persistence, which may contribute to the immature phenotype of the DCs and incomplete activation of naïve F5 cells. During this time mRNA levels for several inflammatory chemokines remain elevated in the lungs and DLNs including CCL8 and CXCL9. Consistent with this, naïve F5 cells lacking CXCR3 and CCR2 chemokine receptors show impaired proliferative responses when transferred to influenza infected mice 30dpi, as compared to wild type cells. These data indicate that a mild inflammatory response is induced during antigen persistence and supports chronic activation of naïve CD8 T cells through local chemokine expression.