LYMPHOID CELL MIGRATION BETWEEN DISTANT LYMPH NODES IN MICE

Abstract

Migration, circulation and recirculation of lymphocytes are important features of
the immunologically active system (review: 1). While the existence of such a cell traffic between various lympho-reticular organs via the lymph and blood stream is well established the magnitude of this process with respect to 1) different types of lymphocytes, 2) readily and less readily mobilizable pools af lymphoid cells (2) and 3) inter-organ exchange, needs further clarification.

Lymphoid cell migration from the blood to lymph nodes and back to the blood by lymphatic vessels has been studied in mammals by different labeling techniques and thoracic duct drainage (review: 3). In larger animals canulation of the efferent lymphatics of peripheral lymph nodes can be used successfully for similar purposes (4). Other methods suitable for studying cell migration include 1. extracorporeal irradiation of the circulating blood (5) or lymph (6); 2. shielding of lymphoreticular organs during ionizing whole body irradiation (7), or local irradiation; 3. temporary clamping of blood vessels during in vivo labeling with radioactive substances (review: 8); 4. parabiosis between labeled and unlabeled partners (9, 10); 5. injection of radioactively (11) or chromosomally (10) labeled lymphoid cells obtained from particular organs; and 6. regional labeling of lymphoreticular organs with thymidine_3H (12) or other tritiated nucleosides (13). 

Each of these methods presents particular advantages and disadvantages. For instance, thoracic duct drainage in small animals may introduce complicating factors such as additional stress: handling of cells in vitro may be harmful for specially sensitive elements; injection of cells does not necessarily simulate natural circulation; labeling with thymidine-3H will mark only those cells which during availability of the radioactive precursor are in DNA synthesis: cells with marker chromosomes are only recognizable while in mitosis. 

The present study was undertaken to evaluate in mice the magnitude of lymphocyte exchange between distant lymph nodes with as little interference with physiological conditions as possible. Cytidine-3H was injected into the foot pad of a hind leg in an attempt to obtain preferential labeling of the regional lymph nodes, and the appearance of more heavily labeled lymphoid cells in the contralateral axillary lymph node was followed as a function of time after application of the radioactive nucleoside. Although cytidine-3H may serve as a precursor of both DNA and RNA and, therefore, is not ideal for stable cell labeling, it was chosen because, unlike thymidine-3H (14), it can readily be incorporated into small lymphocytes.