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Characterizing T Cell Movement within Lymph Nodes in the Absence of Antigen¹

Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545

The recent application of two-photon microscopy to the visualization of T cell movement has presented trajectories of individual T cells within lymphoid organs both in the presence and in the absence of Ag-loaded dendritic cells. Remarkably, even though T cells largely move along conduits of the fibroblastic reticular cell network, they appear to execute random walks in lymphoid organs rather than chemotaxis. In this study, we analyze experimental trajectories of T cells using computer simulations of idealized random walks. Comparisons of simulations with experimental data provide estimates of key parameters that characterize T cell motion in vivo. For example, we find that the distance moved before turning is about twice the distance between intersections in the fibroblastic reticular cell network, suggesting that at an intersection a T cell will turn onto a new fiber 50% of the time. Although the calibrated model appears to offer an accurate representation of T cell movement, it has also uncovered inconsistencies across different experimental data sets.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was performed under the auspices of the U.S. Department of Energy under Contract DE-AC52-06NA25396 and supported in part by Mathematics of Information Technology and Complex Systems (to C.B.), University of New Mexico/Los Alamos National Laboratory Joint Science and Technology Laboratory (to C.B.), and National Institutes of Health Grants R37-AI28433, R01-RR06555, and P01-AI071195 (to A.S.P.).

² Current address: Department of Chemical Engineering, Indian Institute of Science, Bangalore, India.

³ Address correspondence and reprint requests to Dr. Alan S. Perelson, Los Alamos National Laboratory, MS K710, T-10, Los Alamos, NM 87545. E-mail address: asp{at}lanl.gov

⁴ Abbreviations used in this paper: FCR, fibroblastic reticular cell; SSR, sum of the squared residuals.