T-cell motility in the early stages of the immune response modeled as a random walk amongst targets.
The transport process by which a T cell makes high-frequency encounters with antigen-presenting cells following infection is an important element of adaptive immunity. Recent experimental work has allowed in vivo cell motility to be characterized in detail. On the basis of experimental data we develop a quantitative model for encounters between T cells and antigen-presenting cells. We model this as a transport-limited chemical reaction with the dynamics dependent on physical contact between randomly moving reactants. We use asymptotic methods to calculate a time distribution which characterizes the delay before a T cell is activated and use Monte Carlo simulations to verify the analysis. We find that the density of antigen-primed dendritic cells within the lymph node paracortex must be greater than 35 cells/mm3 for a T cell to have a more than 50% chance of encountering a dendritic cell within 24 h. This density is much larger than existing estimates based on calculations which neglect the transport process. We also use simulations to compare a T cell which re-orients isotropically with a T cell which turns according to an experimentally observed distribution and find that the effects of anisotropy on the solution are small.
Preston
S P
SP
Centre for Mathematical Medicine, School of Mathematical Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
Waters
S L
SL
Jensen
O E
OE
Heaton
P R
PR
Pritchard
D I
DI
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000276:immunology; D003198:Computer Simulation; D003713:Dendritic Cells / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D018448:Models, Immunological; D015233:Models, Statistical; D013269:Stochastic Processes; D013601:T-Lymphocytes / Q000276:immunology*
D000949:Histocompatibility Antigens Class II