Analyzing the Migration of Labeled T Cells In Vivo: An Essential Approach with Challenging Features

Abstract

SUMMARY:T cells are involved in the pathogenesis of many diseases. To exert a pathological effect, T cells enter the tissues.We show that the determination of their entry site requires isolation of the respective T cell population, injection into genetically un-manipulated animals, and identification of the cells in vivo at various time points after injection. We indicate variables influencing in vivo migration experiments artificially, and outline how resulting problems can be either avoided or taken into account. Reviewing experiments performed according to the outlined criteria reveals two types of migration patterns for T cell subsets in vivo: 1) Naïve and memory T cells enter lymphoid and non-lymphoid organs in comparable numbers, but selectively accumulate in lymphoid tissues over time, 2) Effector T cells, too, enter lymphoid and non-lymphoid organs in comparable numbers. However, most of them die within 24 hours. Depending on the presence of cytokines, chemokines and extracellular matrix compounds they are able to survive, thereby preferentially accumulating in their target tissues. This information might help to understand the role of migration in the pathogenesis of T cell mediated diseases. (Lab Invest 2003, 83:459 -469).

Estimating In Vivo Death Rates of Targets due to CD8 T-Cell-Mediated Killing

“…Additional indirect evidence of low survival of splenocytes comes from the observation that generally only 10% or less of adoptively transferred lymphocytes (or splenocytes) are recovered in the spleen and major lymph nodes of recipient mice (26,50). This is in contrast with TDLs, sampled from the lymph and therefore expected to undergo less mechanical death, since up to 80 to 90% of TDLs are recovered after adoptive transfer in rats (39,46,47). In the spleen, unpulsed and pulsed targets die due to preparation-induced death rate ε and pulsed targets also die due to CD8 T-cellmediated killing, described by the rate K. The model equations are…”

“…The route of recirculation of splenocytes in mice has not been thoroughly investigated, however. Migration of radioactively labeled lymphocytes, mainly thoracic duct lymphocytes (TDLs), from the blood to different organs and back to blood has been extensively studied in rats and sheep (22,38,39,45,47) but may be different from that of splenocytes (38,39). Based on previous studies, it is expected that many splenocytes enter the spleen (22,39), one of the major lymphoid organs (24).…”

Lymphocyte numbers and subsets in the human blood

“…The migration pathways of lymphocytes vary, depending on their distinct functions (for review see [28][29][30][31]). Several molecules and chemokines are involved in this process.…”

Mathematical Modeling Reveals Kinetics of Lymphocyte Recirculation in the Whole Organism

“…Naive, antigen-unexperienced lymphocytes are traditionally thought to recirculate mainly between blood, lymph, and secondary lymphoid organs such as spleen, lymph nodes, and Peyer's patches [2], [4], [5]. Effector and memory lymphocytes can access nonlymphoid tissues such as the brain, skin, lung, vaginal tract, salivary gland, and gut epithelium [6]–[15]. Although receptors and their ligands regulating entrance of lymphocytes into various lymphoid or nonlymphoid tissues have been thoroughly studied [16]–[20], how quickly lymphocytes can enter a particular tissue and how long they will stay in that tissue remains incompletely understood.…”

“…The number of lymphocytes found in a particular tissue results from several different processes: entrance of lymphocytes in the tissue, lymphocyte proliferation in the tissue, lymphocyte death in the tissue, and lymphocyte exit from the tissue [6]. Change in either of these processes, for example, during an infection, will change the number of lymphocytes residing in the tissue.…”