Memory T-helper Cells Research Articles

Expression of the G-protein--coupled receptor BLR1 defines mature, recirculating B cells and a subset of T-helper memory cells

The G-protein-coupled receptor BLR1 related to receptors for chemokines and neuropeptides has been identified as the first lymphocyte-specific member of the gene family characterized by seven transmembrane-spanning regions. Using a high-affinity anti-BLR1 monoclonal antibody (MoAb) and three-color flow cytometry it is shown that BLR1 expression on peripheral blood cells is limited to B cells and to a subset of CD4+ (14%) and CD8+ (2%) lymphocytes. T cells expressing BLR1 were positive for CD45R0, were negative for interleukin-2 receptors, show high levels of CD44, and show low levels of L-selectin. The majority of CD4+ cells originating from secondary lymphatic tissue, but none of cord blood- derived T cells, express BLR1. These observations suggest that BLR1 is a marker for memory T cells. Furthermore, BLR1 expression was detected on all CD19+ peripheral or tonsillar B lymphocytes, but only on a fraction of cord blood cells and bone marrow cells expressing CD19, sIgM, or sIgD. Interestingly, activation of both mature B and T cells by CD40 MoAb and CD3 MoAb, respectively, led to complete downregulation of BLR1. These data suggest that the G-protein-coupled receptor BLR1 is involved in functional control of mature recirculating B cells and T- helper memory cells participating in cell migration and cell activation.

Expression of the G-Protein-Coupled Receptor BLR1 Defines Mature, Recirculating B Cells and a Subset of T-Helper Memory Cells

The G-protein-coupled receptor BLR1 related to receptors for chemokines and neuropeptides has been identified as the first lymphocyte-specific member of the gene family characterized by seven transmembrane-spanning regions. Using a high-affinity anti-BLR1 monoclonal antibody (MoAb) and three-color flow cytometry it is shown that BLR1 expression on peripheral blood cells is limited to B cells and to a subset of CD4+ (14%) and CD8+ (2%) lymphocytes. T cells expressing BLR1 were positive for CD45R0, were negative for interleukin-2 receptors, show high levels of CD44, and show low levels of L-selectin. The majority of CD4+ cells originating from secondary lymphatic tissue, but none of cord blood-derived T cells, express BLR1. These observations suggest that BLR1 is a marker for memory T cells. Furthermore, BLR1 expression was detected on all CD19+ peripheral or tonsillar B lymphocytes, but only on a fraction of cord blood cells and bone marrow cells expressing CD19, sIgM, or sIgD. Interestingly, activation of both mature B and T cells by CD40 MoAb and CD3 MoAb, respectively, led to complete downregulation of BLR1. These data suggest that the G-protein-coupled receptor BLR1 is involved in functional control of mature recirculating B cells and T-helper memory cells participating in cell migration and cell activation.

The LFA‐3 Adhesion Pathway is Differently Utilized by Superantigen‐Activated Human CD4+ T‐Cell Subsets

The superantigen SEA binds to MHC class II molecules and activates a large fraction of T cells as a result of interaction with particular TCR-V beta sequences. MHC class II transfected CHO cells induce a marginal CD4+ T-cell proliferation in the presence of SEA. CHO cells transfected with both MHC class II and LFA-3 (HLA-DR4/LFA-3 double transfectants) supported a vigorous T-cell proliferation and required 1000-fold lower SEA concentration than DR4-transfected cells. DR4/LFA-3 double transfectants presenting SEA to CD4+ T cells induced large amounts of IFN-gamma, while single DR4 transfectants failed to elicit IFN-gamma production. CD4+45RA+ naive T cells proliferated much more strongly compared with CD4+45R0+ memory T cells when SEA was presented by the DR4/LFA-3-transfected cells. In contrast, IFN-gamma production was only detected in CD4+45R0+ memory cells. The enhanced proliferation by the CD4+45RA+ naive T cells was not due to a stronger binding to the accessory DR4/LFA-3 cells. Human CD4+ T-cell lines mediated a low level of SEA-dependent cell-mediated cytotoxicity (SDCC) against DR4 target cells, whereas a strong SDCC was mediated against DR4/LFA-3-expressing target cells. These results demonstrate that superantigen-activated human CD4+ T cells require the adhesion molecule LFA-3 for optimal stimulation and that the CD4+ naive and memory T-helper cells are different in their response to LFA-3 as an accessory molecule.