Lymphocyte homing receptors

Gallatin, Michael; John, Thomas P. St.; Siegelman, Mark H.; Reichert, Roger A.; Butcher, Eugene C.; Weissman, Irving L.

doi:10.1016/0092-8674(86)90832-9

Cited by 240 publications

(116 citation statements)

References 55 publications

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“…Many models of leukocyte-endothelial cell recognition preceding transendothelial migration of leukocytes have been characterized as a multistep process involving reversible adhesion, leukocyte activation, and activation-dependent binding (2,19,20,(41)(42)(43)(44)(45). In this study, we show that integrin ␣ 4 -positive and CD44-positive activated T cells with different in vivo functions can enter the brain of naive mice.…”

Section: Discussionmentioning

confidence: 77%

Antibodies to CD44 and integrin α₄, but not L-selectin, prevent central nervous system inflammation and experimental encephalomyelitis by blocking secondary leukocyte recruitment

Brocke

Piercy

Steinman

et al. 1999

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

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269

187

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The role of various adhesion molecules in lymphocyte homing to the brain and in inf lammatory autoimmune disease of the central nervous system (CNS) was examined in mice. Activated T cell lines and clones expressed CD44 and integrin ␣ 4 , but not L-selectin, and entered the CNS independent of their antigen specificity. mAbs directed against CD44 and integrin ␣ 4 prevented the transfer of experimental autoimmune encephalomyelitis (EAE) by myelin basic protein-specific T cells. T cells preincubated with anti-CD44 or antiintegrin ␣ 4 were blocked only partially from entering the brain parenchyma. However, both antibodies efficiently prevented CNS inf lammation and clinical expression of EAE when injected in vivo. This effect lasted as long as antibodies were administered. Antibodies specific for Lselectin had no effect on homing of encephalitogenic T cells to the brain or development of EAE. Antiintegrin ␣ 4 and anti-CD44 did not impair the activation and function of encephalitogenic T cells in vitro and did not deplete integrin ␣ 4 -or CD44-positive cells in vivo. These data suggest that, in the absence of leukocyte recruitment, the entry of a reduced number of activated myelin basic protein-reactive T cells in the CNS is not sufficient for the development and expression of EAE. We propose that antibodies to integrin ␣ 4 and CD44 prevent clinical disease by partially targeting the primary inf lux of encephalitogenic T cells and by preventing the secondary inf lux of leukocytes to lesions initiated by the transferred T cells.

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Section: Discussionmentioning

confidence: 77%

Antibodies to CD44 and integrin α₄, but not L-selectin, prevent central nervous system inflammation and experimental encephalomyelitis by blocking secondary leukocyte recruitment

Brocke

Piercy

Steinman

et al. 1999

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

Self Cite

269

187

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“…gp90HR Ka " T «> is indistinguishable from CD44(Pgp-1) antigen (8)(9)(10)(11)(12)(13)(14)(15)(16); this report) Although human gp90HR Herm8S shares MEL-14 antibody epitope with mouse gp90HR MEL14 they are structurally distinct (7,(17)(18)(19)(20). Both gp90HRs appear to mediate specific binding for endothelium and have therefore been implicated in T and B lymphocyte traffic (6,7) It is generally assumed that gp90HRs are acquired during B and T cell development in bone marrow and thymus respectively (6), and that CD44 in normal human thymus is associated with thymocyte functional maturation and location in the medulla (14) In spite of this knowledge, very little is known about the role of such receptors (and their ligands) in T cell precursor migration, commitment to T cell lineage, and intrathymic cell traffic. Here we entertain the hypothesis that acquisition of the gp90HR, as recognized by CD44 antibodies, precedes T cell differentiation in the thymus, and might play a role in early T cell development.…”

Section: Introductionmentioning

confidence: 91%

Function of CD44(Pgp-1) homing receptor in human T cell precursors

Hera¹,

Acevedo²,

Marston³

et al. 1989

Int Immunol

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T cell precursors migrate from extrathymlc hematopoietic tissues and differentiate after encountering the thymic mlcroenvlronment. We asked whether human T cell precursors express the CD44(Pgp-1/gp90HR) class of homing receptors that have been implicated in the traffic of hematopoietic cells, such as lymphocyte entry to peripheral lymphoid organs. Flow cytometry and immunopreclpltatlon studies demonstrate that CD7+34+, CD1 -2-3-4-8-14-16-20-cells In bone marrow and thymus, which have been shown to exhibit features of T cell precursors, bear CD44. Immunohlstologlcal studies show that clusters of thymocytes in the subcapsular and the Inner cortex and most medullary thymocytes are clearly CD44 + , whereas the expression of CD44 is selectively downregulated in CD3-and CD3 low functionally Incompetent cortical thymocytes. The expression of CD44 Is not restricted to T cell precursors but also occurs In thymic stroma, which bear a different molecular species of CD44. CD44-specific antibodies exert stimulatory effects on T cell precursors, a process that is dependent on stromal cells. We postulate that CD44 might be an adhesion molecule for precursor homing to thymus and that it participates In cell-to-cell interactions within the thymic environment.

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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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Lymphocyte homing receptors

Cited by 240 publications

References 55 publications

Antibodies to CD44 and integrin α₄, but not L-selectin, prevent central nervous system inflammation and experimental encephalomyelitis by blocking secondary leukocyte recruitment

Antibodies to CD44 and integrin α₄, but not L-selectin, prevent central nervous system inflammation and experimental encephalomyelitis by blocking secondary leukocyte recruitment

Function of CD44(Pgp-1) homing receptor in human T cell precursors

How One Thing Led to Another

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Lymphocyte homing receptors

Cited by 240 publications

References 55 publications

Antibodies to CD44 and integrin α4, but not L-selectin, prevent central nervous system inflammation and experimental encephalomyelitis by blocking secondary leukocyte recruitment

Antibodies to CD44 and integrin α4, but not L-selectin, prevent central nervous system inflammation and experimental encephalomyelitis by blocking secondary leukocyte recruitment

Function of CD44(Pgp-1) homing receptor in human T cell precursors

How One Thing Led to Another

Contact Info

Product

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About

Antibodies to CD44 and integrin α₄, but not L-selectin, prevent central nervous system inflammation and experimental encephalomyelitis by blocking secondary leukocyte recruitment

Antibodies to CD44 and integrin α₄, but not L-selectin, prevent central nervous system inflammation and experimental encephalomyelitis by blocking secondary leukocyte recruitment