Expansion Of Memory CD8 Research Articles

Memory CD8+ T cells are required for protection from persistent hepatitis C virus infection.

Few hepatitis C virus (HCV) infections resolve spontaneously but those that do appear to afford protective immunity. Second infections are usually shorter in duration and are less likely to persist but mechanisms of virus control in immune individuals have not been identified. In this study we investigated whether memory helper and/or cytotoxic T lymphocytes provide protection in chimpanzees serially reinfected with the virus. Clearance of the first infection took 3–4 mo and coincided with the delayed onset of CD4+ and CD8+ T cell responses. High frequencies of memory T cells targeting multiple HCV proteins were stable over 7 yr of follow-up. Animals were infected for a second time to assess the protective role of memory T cells. In contrast to the prolonged course of the first infection, viremia was terminated within 14 d. Control of this second infection was kinetically linked to rapid acquisition of virus-specific cytolytic activity by liver resident CD8+ T cells and expansion of memory CD4+ and CD8+ T cells in blood. The importance of memory CD8+ T cells in control of HCV infection was confirmed by antibody-mediated depletion of this lymphocyte subset before a third infection. Virus replication was prolonged despite the presence of memory CD4+ T helper cells primed by the two prior infections and was not terminated until HCV-specific CD8+ T cells recovered in the liver. These experiments demonstrate an essential role for memory CD8+ T cells in long-term protection from chronic hepatitis C.

CCR7 Ligands Induced Expansion of Memory CD4+ T Cells and Protection from Viral Infection

Background: CC chemokine receptor (CCR) 7 and cognate CCR7 ligands, CCL21 (formerly secondary lymphoid tissue chemokine [SLC]) and CCL19 (formerly Epstein-Barr virus-induced molecule 1 ligand chemokine [ELC]), were known to establish microenvironment for the initiation of immune responses in secondary lymphoid tissue. As described previously, coadministration of DNA vaccine with CCR7 ligand-encoding plasmid DNA elicited enhanced humoral and cellular immunity via increasing the number of dendritic cells (DC) in secondary lymphoid tissue. The author hypothesized here that CCR7 ligand DNA could effectively expand memory CD4+ T cells to protect from viral infection likely via increasing DC number. Methods: To evaluate the effect of CCR7 ligand DNA on the expansion of memory CD4+ T cells, DO11.10.BALB/c transgenic (Tg)-mice, which have highly frequent ovalbumin (OVA)323-339 peptide-specific CD4+ T cells, were used. Tg-mice were previously injected with CCR7 ligand DNA, then immunized with OVA323-339 peptide plus complete Freund's adjuvant. Subsequently, memory CD4+ T cells in peripheral blood lymphocytes (PBL) were analyzed by FACS analysis for memory phenotype (CD44 and CD62 L) at memory stage. Memory CD4+ T cells recruited into inflammatory site induced with OVA-expressing virus were also analyzed. Finally, the protective efficacy against viral infection was evaluated. Results: CCR7 ligand DNA-treated Tg-mice showed more expanded CD44 memory CD4+ T cells in PBL than control vector-treated animals. The increased number of memory CD4+ T cells recruited into inflammatory site was also observed in CCR7 ligand DNA-treated Tg-mice. Such effectively expanded memory CD4+ T cell population increased the protective immunity against virulent viral infection. Conclusion: These results document that CCR7 and its cognate ligands play an important role in intracellular infection through establishing optimal memory T cell. Moreover, CCR7 ligand could be useful as modulator in DNA vaccination against viral infection as well as cancer. (Im m une N etw ork 2003;3(1):29-37)