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M S Asano

Publications and source records attributed to M S Asano.

4 recordsLinked to original sources
PubMed1998

Long-term CD4 Th1 and Th2 memory following acute lymphocytic choriomeningitis virus infection.

CD4 T cells play a central role in viral immunity. They provide help for B cells and CD8 T cells and can act as effectors themselves. Despite their importance, relatively little is known about the magnitude and duration of virus-specific CD4 T-cell responses. In particular, it is not known whether both CD4 Th1 memory and CD4 Th2 memory can be induced by viral infections. To address these issues, we quantitated virus-specific CD4 Th1 (interleukin 2 [IL-2] and gamma-interferon) and Th2 (IL-4) responses in mice acutely infected with lymphocytic choriomeningitis virus (LCMV). Using two sensitive assays (enzyme-linked immunospot assay and intracellular stain) to measure cytokine production at the single-cell level, we found that both CD4 Th1 and Th2 responses were induced during primary LCMV infection. At the peak (day 8) of the response, the frequency of LCMV-specific CD4 Th1 cells was 1/35 to 1/160 CD4 T cells, and the frequency of Th2 cells was 1/400. After viral clearance, the numbers of virus-specific CD4 T cells dropped to 1/260 to 1/3,700 and then were maintained at this level indefinitely. Upon rechallenge with LCMV, both CD4 Th1 and Th2 memory cells made an anamnestic response in vivo. These results show that unlike some microbial infections in which only Th1 or Th2 responses are seen, an acute viral infection can induce a mixed CD4 T-cell response with long-term memory.

Animals↗
PubMed1996

CD8 T cell memory in B cell-deficient mice.

Antigen presentation by B cells and persistence of antigen-antibody complexes on follicular dendritic cells (FDC) have been implicated in sustaining T cell memory. In this study we have examined the role of B cells and antibody in the generation and maintenance of CD8+ cytotoxic T lymphocyte (CTL) memory. To address this issue we compared CTL responses to lymphocytic choriomeningitis virus (LCMV) in normal (+/+) versus B cell-deficient mice. The CTL response to acute LCMV infection can be broken down into three distinct phases: (a) the initial phase (days 3-8 after infection) of antigen-driven expansion of virus-specific CD8+ T cells and the development of effector CTL (i.e., direct ex vivo killers); (b) a phase of death (between days 10 and 30 after infection) during which >95% of the virus-specific CTL die and the direct effector activity subsides; and (c) the phase of long-term memory (after day 30) that is characterized by a stable pool of memory CTL that persist for the life span of the animal. The role of B cells in each of these three phases of the CTL response was analyzed. We found that B cells were not required for the expansion and activation of virus-specific CTL. The kinetics and magnitude of the effector CTL response, as measured by direct killing of infected targets by ex vivo isolated splenocytes, was identical in B cell-deficient and +/+ mice. Also, the expansion of CD8+ T cells was not affected by the absence of B cells and/or antibody; in both groups of mice there was an approximately 10,000-fold increase in the number of LCMV-specific CTL and a greater than 10-fold increase in the total number of activated (CD44hi) CD8+ T cells during the first week after virus infection. Although no differences were seen during the "expansion" phase, we found that the "death" phase was more pronounced in B cell-deficient mice. However, this increased cell death was not selective for LCMV-specific CTL, and during this period the total number of CD8+ T cells also dropped substantially more in B cell-deficient mice. As a result of this, the absolute numbers of LCMV-specific CTL were lower in B cell-deficient mice but the frequencies were comparable in both groups of mice. More significantly, the memory phase of the CTL response was not affected by the absence of B cells and a stable number of LCMV-specific CTL persisted in B cell-deficient mice for up to 6 mo. Upon reinfection, B cell-deficient mice that had resolved an acute LCMV infection were able to make accelerated CTL responses in vivo and eliminated virus more efficiently than naive B cell-deficient mice. Thus, CTL memory, as assessed by frequency of virus-specific CTL or protective immunity, does not decline in the absence of B cells. Taken together, these results show that neither B cells nor antigen-antibody complexes are essential for the maintenance of CD8+ CTL memory.

Animals↗
PubMed1995

DNA vaccination against persistent viral infection.

This study shows that DNA vaccination can confer protection against a persistent viral infection by priming CD8+ cytotoxic T lymphocytes (CTL). Adult BALB/c (H-2d) mice were injected intramuscularly with a plasmid expressing the nucleoprotein (NP) gene of lymphocytic choriomeningitis virus (LCMV) under the control of the cytomegalovirus promoter. The LCMV NP contains the immunodominant CTL epitope (amino acids 118 to 126) recognized by mice of the H-2d haplotype. After three injections with 200 micrograms of NP DNA, the vaccinated mice were challenged with LCMV variants (clones 13 and 28b) that establish persistent infection in naive adult mice. Fifty percent of the DNA-vaccinated mice were protected, as evidenced by decreased levels of infectious virus in the blood and tissues, eventual clearance of viral antigen from all organs tested, the presence of an enhanced LCMV-specific CD8+ CTL response, and maintenance of memory CTL after clearance of virus infection. However, it should be noted that protection was seen in only half of the vaccinated mice, and we were unable to directly measure virus-specific immune responses in any of the DNA-vaccinated mice prior to LCMV challenge. Thus, at least in the system that we have used, gene immunization was a suboptimal method of inducing protective immunity and was several orders of magnitude less efficient than vaccination with live virus. In conclusion, our results show that DNA immunization works against a persistent viral infection but that efforts should be directed towards improving this novel method of vaccination.

3T3 Cells↗