Different dynamics of CD4+ and CD8+ T cell responses during and after acute lymphocytic choriomeningitis virus infection.
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.
De Boer
Rob J
RJ
Theoretical Biology, Utrecht University, Utrecht, The Netherlands. R.J.DeBoer@bio.uu.nl
Homann
Dirk
D
Perelson
Alan S
AS
D000208:Acute Disease; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D016056:Immunodominant Epitopes / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000821:virology; D013997:Time Factors; D014764:Viral Proteins / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D014764:Viral Proteins