Naive and memory T cells show distinct pathways of lymphocyte recirculation.
In this report, we have addressed two questions concerning immunological memory: the way in which naive and memory T cells recirculate through the body, and the intrinsic rate of division within the naive and memory populations. We identified naive and memory T cells in sheep by their cell surface phenotype and their ability to respond to recall antigen. Memory T cells were CD2hi, CD58hi, CD44hi, CD11ahi, and CD45R-, as pertains in man. T cells that crossed from blood to the tissues of the hind leg and accumulated in the popliteal afferent lymph were all of memory phenotype. Conversely, T cells in efferent lymph, 90% of which entered the lymph node (LN) via high endothelial venules (HEV), were mostly of the naive phenotype (CD2lo, CD58lo, CD44lo, CD11alo, and CD45R+). The marked enrichment of these two phenotypes in different recirculatory compartments indicated that memory T cells selectively traffic from blood to peripheral tissues to LN (via afferent lymph), whereas naive T cells selectively traffic from blood to LN (via HEV). We argue that the differential use of these two recirculation pathways probably optimizes lymphocyte interactions with antigen. The nonrandom distribution of T cell subsets in various recirculatory compartments may be related to the relative proportion of memory cells in each subset. In particular, gamma/delta T cells in blood were almost exclusively of memory phenotype, and accumulated preferentially in afferent, but not in efferent, lymph. Finally, using the bromo-deoxyuridine labeling technique, we found that at least a sizeable proportion of memory T cells, whether in blood or afferent lymph, were a dividing population of cells, whereas naive T cells were a nondividing population. This result supports an alternative model of lymphocyte memory that assumes that maintenance of memory requires persistent antigenic stimulation.
Mackay
C R
CR
Basel Institute for Immunology, Switzerland.
Marston
W L
WL
Dudler
L
L
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001973:Bromodeoxyuridine / Q000378:metabolism; D007156:Immunologic Memory; D008196:Lymph / Q000276:immunology; D008213:Lymphocyte Activation; D010641:Phenotype; D012756:Sheep; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D001973:Bromodeoxyuridine