Activation and increased expression of adhesion molecules on peripheral blood lymphocytes is a mechanism for the immediate lymphocytopenia after administration of OKT3

S Buysmann, F J Bemelman, P T Schellekens, Y van Kooyk, C G Figdor, I J ten Berge

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

We investigated the mechanism by which antihuman CD3 monoclonal antibodies of the isotypes IgG2a (eg, OKT3) and IgA (eg, IXA) can induce the rapid disappearance of virtually all circulating T lymphocytes. We hypothesize that upregulation of adhesion molecules on the lymphocyte membrane contributes to this effect. However, this hypothesis is difficult to test, because of the inherent lymphocytopenia and/or shifts in lymphocyte populations between intra and extra-vascular compartments. Therefore, studies in vitro were performed, as well. Analysis of peripheral blood lymphocytes isolated at several times after addition of OKT3 or IXA to whole blood of healthy individuals showed an immediate increase in the proportion of T cells expressing NKI-L16, an activation epitope on CD11a/CD18. Likewise, an increase in CD11b/CD18 expression occurred. In parallel experiments, a transiently increased adhesion of T cells to endothelial cell monolayers was observed. This adhesion could be completely blocked by anti-CD18 or anti-CD11a monoclonal antibodies and only partly by an anti-CD11b antibody. Our data indicate that upregulation of activation epitopes of CD11a/CD18, as well as increased expression of CD11b/CD18 on T lymphocytes, may result in increased adhesion of these cells to intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 on vascular endothelium. This phenomenon may, at least, partly explain the rapidly occurring peripheral lymphocytopenia observed in vivo.

Original languageEnglish
Pages (from-to)404-11
Number of pages8
JournalBlood
Volume87
Issue number1
Publication statusPublished - 1 Jan 1996

Cite this

@article{43ff5da9218846899de9ee45e79146db,
title = "Activation and increased expression of adhesion molecules on peripheral blood lymphocytes is a mechanism for the immediate lymphocytopenia after administration of OKT3",
abstract = "We investigated the mechanism by which antihuman CD3 monoclonal antibodies of the isotypes IgG2a (eg, OKT3) and IgA (eg, IXA) can induce the rapid disappearance of virtually all circulating T lymphocytes. We hypothesize that upregulation of adhesion molecules on the lymphocyte membrane contributes to this effect. However, this hypothesis is difficult to test, because of the inherent lymphocytopenia and/or shifts in lymphocyte populations between intra and extra-vascular compartments. Therefore, studies in vitro were performed, as well. Analysis of peripheral blood lymphocytes isolated at several times after addition of OKT3 or IXA to whole blood of healthy individuals showed an immediate increase in the proportion of T cells expressing NKI-L16, an activation epitope on CD11a/CD18. Likewise, an increase in CD11b/CD18 expression occurred. In parallel experiments, a transiently increased adhesion of T cells to endothelial cell monolayers was observed. This adhesion could be completely blocked by anti-CD18 or anti-CD11a monoclonal antibodies and only partly by an anti-CD11b antibody. Our data indicate that upregulation of activation epitopes of CD11a/CD18, as well as increased expression of CD11b/CD18 on T lymphocytes, may result in increased adhesion of these cells to intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 on vascular endothelium. This phenomenon may, at least, partly explain the rapidly occurring peripheral lymphocytopenia observed in vivo.",
keywords = "Adult, Antigens, CD/metabolism, CD18 Antigens/biosynthesis, Cell Adhesion/drug effects, Cell Adhesion Molecules/biosynthesis, Endothelium, Vascular/cytology, Female, Graft Rejection/prevention & control, Humans, Immunosuppressive Agents/adverse effects, Intercellular Adhesion Molecule-1/metabolism, Kidney Transplantation, L-Selectin/biosynthesis, Lymphopenia/chemically induced, Macrophage-1 Antigen/biosynthesis, Male, Methylprednisolone/therapeutic use, Middle Aged, Muromonab-CD3/adverse effects, T-Lymphocyte Subsets/cytology",
author = "S Buysmann and Bemelman, {F J} and Schellekens, {P T} and {van Kooyk}, Y and Figdor, {C G} and {ten Berge}, {I J}",
year = "1996",
month = "1",
day = "1",
language = "English",
volume = "87",
pages = "404--11",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "1",

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Activation and increased expression of adhesion molecules on peripheral blood lymphocytes is a mechanism for the immediate lymphocytopenia after administration of OKT3. / Buysmann, S; Bemelman, F J; Schellekens, P T; van Kooyk, Y; Figdor, C G; ten Berge, I J.

In: Blood, Vol. 87, No. 1, 01.01.1996, p. 404-11.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Activation and increased expression of adhesion molecules on peripheral blood lymphocytes is a mechanism for the immediate lymphocytopenia after administration of OKT3

AU - Buysmann, S

AU - Bemelman, F J

AU - Schellekens, P T

AU - van Kooyk, Y

AU - Figdor, C G

AU - ten Berge, I J

PY - 1996/1/1

Y1 - 1996/1/1

N2 - We investigated the mechanism by which antihuman CD3 monoclonal antibodies of the isotypes IgG2a (eg, OKT3) and IgA (eg, IXA) can induce the rapid disappearance of virtually all circulating T lymphocytes. We hypothesize that upregulation of adhesion molecules on the lymphocyte membrane contributes to this effect. However, this hypothesis is difficult to test, because of the inherent lymphocytopenia and/or shifts in lymphocyte populations between intra and extra-vascular compartments. Therefore, studies in vitro were performed, as well. Analysis of peripheral blood lymphocytes isolated at several times after addition of OKT3 or IXA to whole blood of healthy individuals showed an immediate increase in the proportion of T cells expressing NKI-L16, an activation epitope on CD11a/CD18. Likewise, an increase in CD11b/CD18 expression occurred. In parallel experiments, a transiently increased adhesion of T cells to endothelial cell monolayers was observed. This adhesion could be completely blocked by anti-CD18 or anti-CD11a monoclonal antibodies and only partly by an anti-CD11b antibody. Our data indicate that upregulation of activation epitopes of CD11a/CD18, as well as increased expression of CD11b/CD18 on T lymphocytes, may result in increased adhesion of these cells to intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 on vascular endothelium. This phenomenon may, at least, partly explain the rapidly occurring peripheral lymphocytopenia observed in vivo.

AB - We investigated the mechanism by which antihuman CD3 monoclonal antibodies of the isotypes IgG2a (eg, OKT3) and IgA (eg, IXA) can induce the rapid disappearance of virtually all circulating T lymphocytes. We hypothesize that upregulation of adhesion molecules on the lymphocyte membrane contributes to this effect. However, this hypothesis is difficult to test, because of the inherent lymphocytopenia and/or shifts in lymphocyte populations between intra and extra-vascular compartments. Therefore, studies in vitro were performed, as well. Analysis of peripheral blood lymphocytes isolated at several times after addition of OKT3 or IXA to whole blood of healthy individuals showed an immediate increase in the proportion of T cells expressing NKI-L16, an activation epitope on CD11a/CD18. Likewise, an increase in CD11b/CD18 expression occurred. In parallel experiments, a transiently increased adhesion of T cells to endothelial cell monolayers was observed. This adhesion could be completely blocked by anti-CD18 or anti-CD11a monoclonal antibodies and only partly by an anti-CD11b antibody. Our data indicate that upregulation of activation epitopes of CD11a/CD18, as well as increased expression of CD11b/CD18 on T lymphocytes, may result in increased adhesion of these cells to intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 on vascular endothelium. This phenomenon may, at least, partly explain the rapidly occurring peripheral lymphocytopenia observed in vivo.

KW - Adult

KW - Antigens, CD/metabolism

KW - CD18 Antigens/biosynthesis

KW - Cell Adhesion/drug effects

KW - Cell Adhesion Molecules/biosynthesis

KW - Endothelium, Vascular/cytology

KW - Female

KW - Graft Rejection/prevention & control

KW - Humans

KW - Immunosuppressive Agents/adverse effects

KW - Intercellular Adhesion Molecule-1/metabolism

KW - Kidney Transplantation

KW - L-Selectin/biosynthesis

KW - Lymphopenia/chemically induced

KW - Macrophage-1 Antigen/biosynthesis

KW - Male

KW - Methylprednisolone/therapeutic use

KW - Middle Aged

KW - Muromonab-CD3/adverse effects

KW - T-Lymphocyte Subsets/cytology

M3 - Article

VL - 87

SP - 404

EP - 411

JO - Blood

JF - Blood

SN - 0006-4971

IS - 1

ER -