Cloning and expression of cDNAs for the alpha subunit of the murine lymphocyte-Peyer's patch adhesion molecule.

Neuhaus, Heinz; Hu, Mickey C.T.; Hemler, Martin E.; Takada, Yoshikazu; Holzmann, Bernhard; Weissman, Irving L.

doi:10.1083/jcb.115.4.1149

Cited by 57 publications

(23 citation statements)

References 45 publications

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“…As shown in Fig. 3, the decrease in the level of u4 transcripts can already be seen at 24 h of PMA stimulation, As previously demonstrated, the a4 probing yields two distinct RNA bands [19], both of which decreased on PMA treatment. Concomitantly a clear increase in the amount of /I, transcript was observed, correlating to the increased total protein levels.…”

Section: R~~~~~~~~ Of Vla-i Eqwdm At the Rna Eevdsupporting

confidence: 56%

Down‐regulation of monocytic VLA‐4 leads to a decreased adhesion to VCAM‐1

Tiisala¹,

Hakkarainen²,

Majuri³

et al. 1993

FEBS Letters

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The ~9, integrin VLA-4 is expressed on practically all leukocytes, except on mature granulocytes. Here we show that in vitro treatment of monocytic cells with phorbol-12-myristate-13-acetate (PMA) leads to a selective decrease in the VLA-4 u-chain expression, both at the RNA and protein level. Meanwhile the expression of/?, and that of a,, another a-chain associating with& was se-en to increase. The decrease of a, expression was restricted to monocytic cells, and was not observed on other VLAll-positive cells tested (MOLT-4 T cells and HOS sarcoma cells). The down-regulation of the VLA-4 u-chain was followed by a decreased binding capacity of the cells to recombinant VCAM-1. This data indicates that while previous findings show that the integrindependent adhesion may rapidly be regulated by altering the avidity of the interacting molecules, their quantitative modulation also has a clear impact on adhesion.

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Section: R~~~~~~~~ Of Vla-i Eqwdm At the Rna Eevdsupporting

confidence: 56%

Down‐regulation of monocytic VLA‐4 leads to a decreased adhesion to VCAM‐1

Tiisala¹,

Hakkarainen²,

Majuri³

et al. 1993

FEBS Letters

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“…Only the surviving SP cells upregulated the tissue-homing receptors for LNs [L-selectin, CD62L (57)] and for PP HEVs [integrin α 4 β 7 (58,59)]. During these studies my fellows and I had discovered the homing receptors (59)(60)(61)(62)(63)(64)(65)(66)(67) and the essential regions of lymphoid organs by finding out how to stain tissue sections for cell membrane antigens (31 chains (68)(69)(70). The timing of IgH chain rearrangement occurred in distinct pro-B dividing cells, which was prior to light chain rearrangement in nondividing pre-B cells (68,71).…”

Section: The Thymus Thymic Maturation B Lymphocyte Development Hommentioning

confidence: 99%

How One Thing Led to Another

Weissman

2016

Annu. Rev. Immunol.

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I started research in high school, experimenting on immunological tolerance to transplantation antigens. This led to studies of the thymus as the site of maturation of T cells, which led to the discovery, isolation, and clinical transplantation of purified hematopoietic stem cells (HSCs). The induction of immune tolerance with HSCs has led to isolation of other tissue-specific stem cells for regenerative medicine. Our studies of circulating competing germline stem cells in colonial protochordates led us to document competing HSCs. In human acute myelogenous leukemia we showed that all preleukemic mutations occur in HSCs, and determined their order; the final mutations occur in a multipotent progenitor derived from the preleukemic HSC clone. With these, we discovered that CD47 is an upregulated gene in all human cancers and is a “don't eat me” signal; blocking it with antibodies leads to cancer cell phagocytosis. CD47 is the first known gene common to all cancers and is a target for cancer immunotherapy.

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“…A monotonous phenotype of effector memory cells defined by loss of CD62L expression and acquisition of CD44 predominated the peripheral T-cell pool in recipients of bulk T-cell-replete grafts. Antigen activated T cells lose homing to secondary lymphoid organs by down-regulating CD62L (30) while up-regulating the expression of integrin α4β1, which enable them to home to inflamed tissues whose blood vessels express VCAM-1, the addressin for α4β1 (31)(32)(33)(34). CD62L is the homing receptor necessary to enter secondary lymphoid organs in which productive immune responses are generated (35).…”

Section: Hsc Grafts Enhance Lymphoid Reconstitution and De Novo Regenmentioning

confidence: 99%

Co-transplantation of pure blood stem cells with antigen-specific but not bulk T cells augments functional immunity

Müller

Shashidhar

Küpper

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Impaired immunity is a fundamental obstacle to successful allogeneic hematopoietic cell transplantation. Mature graft T cells are thought to provide protection from infections early after transplantation, but can cause life-threatening graft-vs.-host disease. Human CMV is a major pathogen after transplantation. We studied reactivity against the mouse homologue, murine CMV (MCMV), in lethally irradiated mice given allogeneic purified hematopoietic stem cells (HSCs) or HSCs supplemented with T cells or T-cell subsets. Unexpectedly, recipients of purified HSCs mounted superior antiviral responses compared with recipients of HSC plus unselected bulk T cells. Furthermore, supplementation of purified HSC grafts with CD8 + memory or MCMV-specific T cells resulted in enhanced antiviral reactivity. Posttransplantation lymphopenia promoted massive expansion of MCMV-specific T cells when no competing donor T cells were present. In recipients of pure HSCs, naive and memory T cells and innate lymphoid cell populations developed. In contrast, the lymphoid pool in recipients of bulk T cells was dominated by effector memory cells. These studies show that pure HSC transplantations allow superior protective immunity against a viral pathogen compared with unselected mature T cells. This reductionist transplant model reveals the impact of graft composition on regeneration of host, newly generated, and mature transferred T cells, and underscores the deleterious effects of bulk donor T cells. Our findings lead us to conclude that grafts composed of purified HSCs provide an optimal platform for in vivo expansion of selected antigen-specific cells while allowing the reconstitution of a naive T-cell pool.

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Cloning and expression of cDNAs for the alpha subunit of the murine lymphocyte-Peyer's patch adhesion molecule.

Cited by 57 publications

References 45 publications

Down‐regulation of monocytic VLA‐4 leads to a decreased adhesion to VCAM‐1

Down‐regulation of monocytic VLA‐4 leads to a decreased adhesion to VCAM‐1

How One Thing Led to Another

Co-transplantation of pure blood stem cells with antigen-specific but not bulk T cells augments functional immunity

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