(B) MP-IVM micrographs of Treg cells in MC38 tumors in zDC DTR bone marrow chimeras. p values calculated by Mann-Whitney U test. Light blue symbols indicate instances of NFAT activation following a state of inactivity. Numbers in grid indicate quadrant frequencies. (J) Instantaneous NFAT SI as a function of distance to nearest APC. (I) Instantaneous cell velocities with NFAT inactive (NFAT SI ≤0.5) or active (NFAT SI >0.5). Values above graphs refer to frequencies of cells in which NFAT >0.5 for greater than 20% of time. (H) Fraction of time in which NFAT SI >0.5 in individual cell tracks. Numbers in (G) refer to percentages of NFAT SI >0.5. (E–G) 3D-instantaneous migratory velocities (E), arrest coefficient (F), and instantaneous NFAT SI frequency distribution (G) of Treg (n = 1,088 from 25 cells) and Th cells (n = 1,213 from 31 cells) from 3 individual movies each recorded in 2 independent experiments. Migratory tracks indicate 1-min intervals. Bottom panels show false-color representations of the NFAT signaling index (SI) (see Figures S1F–S1L for details). (C and D) MP-IVM micrographs (top panels) and individual cell images (middle panels) depicting the nucleo-cytoplasmic distribution of NFAT-GFP in an exemplary Treg (C) and Th cell (D) in the TME. (B) Phenotype of adoptively transferred T cells in the TME. Its disruption through CTLA-4-blockade may off-set therapeutic benefits in cancer patients.ĬD28 CTLA-4 MP-IVM NFAT T regulatory cell Treg cell cytotoxic T lymphocyte-associated protein 4 multiphoton intravital microscopy nuclear factor of activated T cells tumor tolerance.Ĭopyright © 2021 Elsevier Inc. Therefore, Treg cells self-regulate through a CTLA-4- and CD28-dependent feedback loop that adjusts their population size to the amount of local co-stimulation. CTLA-4-blockade triggered CD28-dependent Treg cell hyper-proliferation in the TME, and concomitant Treg cell inactivation was required to achieve tumor rejection. Contact instability resulted from CTLA-4-dependent downregulation of co-stimulatory B7-family proteins on cDCs, mediated by Treg cells themselves. Unstable cDC contacts sufficed to sustain Treg cell function, whereas T helper cells were activated during stable interactions. We found that the polyclonal Treg cell repertoire is pre-enriched to recognize antigens presented by tumor-associated conventional dendritic cells (cDCs). Here, we used intravital microscopy to characterize the cellular interactions that provide tumor-infiltrating Treg cells with critical activation signals. Electronic address: + T regulatory (Treg) cells promote immunological tumor tolerance, but how their immune-suppressive function is regulated in the tumor microenvironment (TME) remains unknown. 5 The Center for Immunology and Inflammatory Diseases (CIID), Massachusetts General Hospital, Boston, MA 02114, USA Harvard Medical School, Boston, MA 02115, USA.4 Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697, USA Institute for Immunology, University of California, Irvine, Irvine, CA 92697, USA.3 The Center for Immunology and Inflammatory Diseases (CIID), Massachusetts General Hospital, Boston, MA 02114, USA.Electronic address: 2 The Center for Immunology and Inflammatory Diseases (CIID), Massachusetts General Hospital, Boston, MA 02114, USA Harvard Medical School, Boston, MA 02115, USA. 1 The Center for Immunology and Inflammatory Diseases (CIID), Massachusetts General Hospital, Boston, MA 02114, USA Harvard Medical School, Boston, MA 02115, USA Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697, USA Institute for Immunology, University of California, Irvine, Irvine, CA 92697, USA.Lingering is welcome along an elevated passage courtyard that connects students with the outdoors and the building’s extensive second-level academic amenities. These lounges are the heart of residential life, with sweeping views to Aldrich Park and across the Middle Earth neighborhood.Ĭentrally located along the campus Ring Road, the gateway project preserves vistas and offers diverse pathways to access or pass through Middle Earth. Bridging over the podium, Link Lounge is a central gathering space on each residential floor that unites the towers socially and physically. In the street-level podium, a vibrant dining center supports student wellness with fresh menus and teaching platforms. Two residential towers rise above a mixed use podium and richly landscaped base, echoing the natural form and color of the region’s limestone canyons. The Middle Earth Expansion weaves a new living-learning community into the larger campus fabric.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |