4.6 Article

Different dynamics of CD4+ and CD8+ T cell responses during and after acute lymphocytic choriomeningitis virus infection

Journal

JOURNAL OF IMMUNOLOGY
Volume 171, Issue 8, Pages 3928-3935

Publisher

AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.171.8.3928

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Funding

  1. NCRR NIH HHS [RR06555] Funding Source: Medline
  2. NIAID NIH HHS [AI28433] Funding Source: Medline
  3. NIA NIH HHS [AG00080] Funding Source: Medline

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We fit a mathematical model to data characterizing the primary cellular immune response to lymphocytic choriomeningitis virus. The data enumerate the specific CD8(+) T cell response to six MHC class I-restricted epitopes and the specific CD4(+) T cell responses to two MHC class II-restricted epitopes. The peak of the response occurs around day 8 for CD8(+) T cells and around day 9 for CD4(+) T cells. By fitting a model to the data, we characterize the kinetic differences between CD4(+) and CD8(+) T cell responses and among the immunodominant and subdominant responses to the various epitopes. CD8(+) T cell responses have faster kinetics in almost every aspect of the response. For CD8(+) and CD4(+) T cells, the doubling time during the initial expansion phase is 8 and 11 h, respectively. The half-life during the contraction phase following the peak of the response is 41 h and 3 days, respectively. CD4(+) responses are even slower because their contraction phase appears to be biphasic, approaching a 35-day half-life 8 days after the peak of the response. The half-life during the memory phase is 500 days for the CD4(+) T cell responses and appears to be lifelong for the six CD8(+) T cell responses. Comparing the responses between the various epitopes, we find that immunodominant responses have an earlier and/or larger recruitment of precursors cells before the expansion phase and/or have a faster proliferation rate during the expansion phase.

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