The impact of variation in the number of CD8(+) T-cell precursors on the outcome of virus infection.

We investigated the role of varying the initial number of naive antiviral CTL precursors on the dynamics of LCMV-DOCILE infection. C57BL/6 mice, exhibiting LCMV-specific CTLp frequencies of about 50, are protected against virus persistence over a range of infectious doses up to 10(4) pfu. With 10-fold higher doses, a 100-fold increase in CTLp is required to restore virus control. With doses above 10(6) pfu, elevation of the initial CTLp number leads only to lethal immunopathology. Similarly, a 1000-fold increase in the number of initial naïve CTLp enhances the overall kinetics of virus elimination, but cannot limit early virus spread within the first 48 h after low-dose infection (500 pfu). Increases in initial naïve virus-specific CTLp numbers are of limited benefit in antiviral control. In addition to the number of virus-specific T cells, the time period needed to reach cytolytic effector function is a limiting parameter.

[1]  H. Pircher,et al.  On the role of antigen in maintaining cytotoxic T-cell memory. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Hans Hengartner,et al.  Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice , 1994, Nature.

[3]  R. Zinkernagel,et al.  Protection against immunopathological consequences of a viral infection by activated but not resting cytotoxic T cells: T cell memory without "memory T cells"? , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[4]  R M Zinkernagel,et al.  A critical role for neutralizing-antibody-producing B cells, CD4(+) T cells, and interferons in persistent and acute infections of mice with lymphocytic choriomeningitis virus: implications for adoptive immunotherapy of virus carriers. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[5]  A. McMichael,et al.  Rapid Effector Function in CD8+ Memory T Cells , 1997, The Journal of experimental medicine.

[6]  M. Bevan,et al.  Massive expansion of antigen-specific CD8+ T cells during an acute virus infection. , 1998, Immunity.

[7]  David Gray,et al.  Immunological Memory and Protective Immunity: Understanding Their Relation , 1996, Science.

[8]  H. von Boehmer,et al.  On the cellular basis of immunological T cell memory. , 1995, Immunity.

[9]  R. Welsh,et al.  Cytolytically active memory CTL present in lymphocytic choriomeningitis virus-immune mice after clearance of virus infection. , 1997, Journal of immunology.

[10]  C. Taswell,et al.  Limiting dilution assays for the determination of immunocompetent cell frequencies. I. Data analysis. , 1981, Journal of immunology.

[11]  Peter C. Doherty,et al.  Virus-specific CD8+ T-cell memory determined by clonal burst size , 1994, Nature.

[12]  MHC class I and non-MHC-linked capacity for generating an anti-viral CTL response determines susceptibility to CTL exhaustion and establishment of virus persistence in mice. , 1994, Journal of immunology.

[13]  H. Pircher,et al.  On T Cell Memory: Arguments for Antigen Dependence , 1996, Immunological reviews.

[14]  L M Wahl,et al.  Cytotoxic T lymphocytes and viral turnover in HIV type 1 infection. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[15]  J. Christensen,et al.  Exhaustion of CTL memory and recrudescence of viremia in lymphocytic choriomeningitis virus-infected MHC class II-deficient mice and B cell-deficient mice. , 1996, Journal of immunology.

[16]  R. Welsh,et al.  In vivo state of antiviral CTL precursors. Characterization of a cycling cell population containing CTL precursors in immune mice. , 1995, Journal of immunology.

[17]  M. Cohn,et al.  The Protection: The Unit of Humoral Immunity Selected by Evolution , 1990, Immunological reviews.

[18]  R. Ahmed,et al.  Cytotoxic T-cell memory without antigen , 1994, Nature.

[19]  MHC and non-MHC genes regulate elimination of lymphocytic choriomeningitis virus and antiviral cytotoxic T lymphocyte and delayed-type hypersensitivity mediating T lymphocyte activity in parallel. , 1989, Journal of immunology.

[20]  H. Pircher,et al.  Effector T‐Cell Induction and T‐Cell Memory versus Peripheral Deletion of T Cells , 1993, Immunological reviews.

[21]  D. Moskophidis,et al.  The immune response of the mouse to lymphocytic choriomeningitis virus V. High numbers of cytolytic T lymphocytes are generated in the spleen during acute infection , 1987, European journal of immunology.

[22]  R. Zinkernagel,et al.  Role of virus and host variables in virus persistence or immunopathological disease caused by a non-cytolytic virus. , 1995, The Journal of general virology.

[23]  Rolf M. Zinkernagel,et al.  Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector T cells , 1993, Nature.

[24]  R. Zinkernagel,et al.  T cell-mediated hepatitis in mice infected with lymphocytic choriomeningitis virus. Liver cell destruction by H-2 class I- restricted virus-specific cytotoxic T cells as a physiological correlate of the 51Cr-release assay? , 1986, The Journal of experimental medicine.

[25]  R. Zinkernagel,et al.  Peripheral clonal deletion of antiviral memory CD8+ T cells , 1993, European journal of immunology.

[26]  R M Zinkernagel,et al.  Quantification of lymphocytic choriomeningitis virus with an immunological focus assay in 24- or 96-well plates. , 1991, Journal of virological methods.

[27]  H. Pircher,et al.  Visualization, characterization, and turnover of CD8+ memory T cells in virus-infected hosts , 1996, The Journal of experimental medicine.

[28]  M. Nowak,et al.  Population Dynamics of Immune Responses to Persistent Viruses , 1996, Science.

[29]  G. Bocharov,et al.  Modelling the dynamics of LCMV infection in mice: conventional and exhaustive CTL responses. , 1998, Journal of theoretical biology.