Requirement for CD4 T Cell Help in Maintenance of Memory CD8 T Cell Responses Is Epitope Dependent

Abstract

CD4 Th cells play critical roles in stimulating Ab production and in generating primary or maintaining memory CTL. The requirement for CD4 help in generating and maintaining CTL responses has been reported to vary depending on the vector or method used for immunization. In this study, we examined the requirement for CD4 T cell help in generating and maintaining CTL responses to an experimental AIDS vaccine vector based on live recombinant vesicular stomatitis virus (VSV) expressing HIV Env protein. We found that primary CD8 T cell responses and short-term memory to HIV Env and VSV nucleocapsid (VSV N) proteins were largely intact in CD4 T cell-deficient mice. These responses were efficiently recalled at 30 days postinfection by boosting with vaccinia recombinants expressing HIV Env or VSV N. However, by 60 days postinfection, the memory/recall response to VSV N was lost in CD4-deficient mice, while the recall response HIV Env was partially maintained in the same animals for at least 90 days. This result indicates that there are epitope-specific requirements for CD4 help in the maintenance of memory CD8 T cell responses. Our results also suggest that choice of epitopes might be critical in an AIDS vaccine designed to protect against disease in the context of reduced or declining CD4 T cell help.

The <italic>Mycobacterium bovis</italic> BCG prime-Rv0577 DNA boost vaccination induces a durable Th1 immune response in mice

“…Importantly, compared with vaccination with BCG/protein and BCG alone, BCG/DNA regimen can induce higher levels of IFN-γ and IL-2 which are characteristics of Th1 response. The majority of researches indicated that Th1 immune response is essential for Mtb growth control [37], and the strong Th1 response induced by BCG is favorable to aid the maturation and maintenance of CTL [38], which strongly amplifies CTL responses. Furthermore, Th1 cells mainly develop after intracellular bacteria and some virus infection [39].…”

Immune Response in the Absence of Neurovirulence in Mice Infected with M Protein Mutant Vesicular Stomatitis Virus

“…However, it did induce an antibody response similar to that of the mice infected with wt VSV, most likely due to the systemic spread of virus to peripheral organs, such as the spleen and lymph nodes. Previous studies have shown that wt VSV infection of immunocompetent mice results in the CD4 ϩ T-cell-dependent production of neutralizing IgG antibodies and the induction of a virus-specific cytotoxic T lymphocyte response (9,14,17). Therefore, given the similarity in the antibody responses induced by the rwt and rM51R-M viruses, it is likely that rM51R-M virus induces T-cell and memory responses comparable to those observed with wt VSV strains.…”

Expressing human interleukin-15 from oncolytic vesicular stomatitis virus improves survival in a murine metastatic colon adenocarcinoma model through the enhancement of anti-tumor immunity

“…We then investigated CD8 þ T-cell responses vs the tumor (AH1 endogenous MuLV gp70 epitope expressed in CT26 N-SPSYVYHQF-C) 26 and the OV (nucleocapsid epitope N-MPYLIDFGL-C) 27 9 days post-infection. At this time-point, we saw that inclusion of the opt.hIL-15 transgene greatly enhanced anti-tumoral immunity (Figure 4c; Po0.05; Student's t-test), while not modifying the immune response vs the vector (Figure 4d).…”