title: The shedding of CD62L (L-selectin) regulates the acquisition of lytic activity in human tumor reactive T lymphocytes.
abstract: CD62L/L-selectin is a marker found on naïve T cells and further distinguishes central memory (Tcm, CD62L+) from effector memory (Tem, CD62L-) T cells. The regulation of CD62L plays a pivotal role in controlling the traffic of T lymphocytes to and from peripheral lymph nodes. CD62L is shed from the cell membrane following T cell activation, however, the physiological significance of this event remains to be elucidated. In this study, we utilized in vitro generated anti-tumor antigen T cells and melanoma lines as a model to evaluate the dynamics of CD62L shedding and expression of CD107a as a marker of lytic activity. Upon encounter, with matched tumor lines, antigen reactive T cells rapidly lose CD62L expression and this was associated with the acquisition of CD107a. By CD62L ELISA, we confirmed that this transition was mediated by the shedding of CD62L when T cells encountered specific tumor antigen. The introduction of a shedding resistant mutant of CD62L into the tumor antigen-reactive T cell line JKF6 impaired CD107a acquisition following antigen recognition and this was correlated with decreased lytic activity as measured by (51)Cr release assays. The linkage of the shedding of CD62L from the surface of anti-tumor T cells and acquisition of lytic activity, suggests a new function for CD62L in T cell effector functions and anti-tumor activity.
authors.affiliation: Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Shicheng
authors.initials: S
authors.lastname: Yang
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Qiong J
authors.initials: QJ
authors.lastname: Wang
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: Richard A
authors.initials: RA
authors.lastname: Morgan
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007156:Immunologic Memory; D019041:L-Selectin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D052118:Lysosomal-Associated Membrane Protein 1; D019041:L-Selectin