A comparison of random vs. chemotaxis-driven contacts of T cells with dendritic cells during repertoire scanning.
Generating adaptive immunity after infection or immunization requires physical interactions within a lymph node (LN) T-zone between antigen-bearing dendritic cells (DCs) that arrive from peripheral tissues and rare cognate T cells entering via high endothelial venules (HEVs). This interaction results in activation of cognate T cells, expansion of that T cell lineage and their exit from the LN T-zone via efferent lymphatics (ELs). How antigen-specific T cells locate DCs within this complex environment is controversial, and both random T cell migration and chemotaxis have been proposed. We developed an agent-based computational model of a LN that captures many features of T cell and DC dynamics observed by two-photon microscopy. Our simulations matched in vivo two-photon microscopy data regarding T cell speed, short-term directional persistence of motion and cell motility. We also obtained in vivo data regarding density of T cells and DCs within a LN and matched our model environment to measurements of the distance from HEVs to ELs. We used our model to compare chemotaxis with random motion and showed that chemotaxis increased total number of T cell DC contacts, but decreased unique contacts, producing fewer activated T cells. Our results suggest that, within a LN T-zone, a random search strategy is optimal for a rare cognate T cell to find its DC match and maximize production of activated T cells.
Riggs
Thomas
T
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-0620, USA.
Walts
Adrienne
A
Perry
Nicolas
N
Bickle
Laura
L
Lynch
Jennifer N
JN
Myers
Amy
A
Flynn
Joanne
J
Linderman
Jennifer J
JJ
Miller
Mark J
MJ
Kirschner
Denise E
DE
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D018448:Models, Immunological; D012680:Sensitivity and Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology*