T Lymphocyte Migration to Lymph Nodes Is Maintained during Homeostatic Proliferation

Abstract The immune system maintains appropriate cell numbers through regulation of cell proliferation and death. Normal tissue distribution of lymphocytes is maintained through expression of specific adhesion molecules and chemokine receptors such as L-selectin and CCR7, respectively. Lymphocyte insufficiency or lymphopenia induces homeostatic proliferation of existing lymphocytes to increase cell numbers. Interestingly, homeostatic proliferation of T lymphocytes induces a phenotypic change from naïve- to memory-type cell. Naïve T cells recirculate between blood and lymphoid tissues whereas memory T cells migrate to nonlymphoid sites such as skin and gut. To assess effects of homeostatic proliferation on migratory ability of T cells, a murine model of lymphopenia-induced homeostatic proliferation was used. Carboxyfluorescein diacetate, succinimidyl ester-labeled wild-type splenocytes were adoptively transferred into recombination activation gene-1-deficient mice and analyzed by flow cytometry,in vitrochemotactic andin vivomigration assays, and immunofluorescence microscopy. Homeostatically proliferated T cells acquired a mixed memory-type CD44^highL-selectin^highCCR7^lowphenotype. Consistent with this, chemotaxis to secondary lymphoid tissue chemokinein vitrowas reduced by 22%–34%. By contrast, no differences were found for migration or entry into lymph nodes duringin vivomigration assays. Therefore, T lymphocytes that have undergone homeostatic proliferation recirculate using mechanisms similar to naïve T cells.