Neural-Cadherin Influences the Homing of Terminally Differentiated Memory CD8 T Cells to the Lymph Nodes and Bone Marrow

Memory T (T-M) cells play an important role in the long-term defense against pathogen reinvasion. However, it is still unclear how these cells receive the crucial signals necessary for their longevity and homeostatic turnover. To understand how T-M cells receive these signals, we infected mice with lymphocytic choriomeningitis virus (LCMV) and examined the expression sites of neural cadherin (N-cadherin) by immunofluorescence microscopy. We found that N-cadherin was expressed in the surroundings of the white pulps of the spleen and medulla of lymph nodes (LNs). Moreover, T-M cells expressing high levels of killer cell lectin-like receptor G1 (KLRG1), a ligand of N-cadherin, were co-localized with N-cadherin(+) cells in the spleen but not in LNs. We then blocked N-cadherin in vivo to investigate whether it regulates the formation or function of T-M cells. The numbers of CD127(hi)CD62L(hi) T-M cells in the spleen of memory P14 chimeric mice declined when N-cadherin was blocked during the contraction phase, without functional impairment of these cells. In addition, when CD127(lo)KLRG1(hi) T-M cells were adoptively transferred into anti- N-cadherin- treated mice compared with control mice, the number of these cells was reduced in the bone marrow and LNs, with-out functional loss. Taken together, our results suggest that N-cadherin participates in the development of CD127(hi)CD62L(hi) T-M cells and homing of CD127(lo)KLRG1(hi) T-M cells to lymphoid organs.