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.

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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

Blood ◽

10.1182/blood.v87.1.404.bloodjournal871404 ◽

1996 ◽

Vol 87 (1) ◽

pp. 404-411 ◽

Cited By ~ 1

Author(s):

S Buysmann ◽

FJ Bemelman ◽

PT Schellekens ◽

Y van Kooyk ◽

CG Figdor ◽

...

Keyword(s):

T Cells ◽

Monoclonal Antibodies ◽

T Lymphocytes ◽

Adhesion Molecules ◽

Peripheral Blood ◽

Peripheral Blood Lymphocytes ◽

Intercellular Adhesion Molecule ◽

Intercellular Adhesion Molecule 1 ◽

Blood Lymphocytes

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.

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Endothelial adhesion molecules and their role in inflammation

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y93-012 ◽

1993 ◽

Vol 71 (1) ◽

pp. 76-87 ◽

Cited By ~ 117

Author(s):

C. Wayne Smith

Keyword(s):

Endothelial Cells ◽

Monoclonal Antibodies ◽

Endothelial Cell ◽

Cell Surface ◽

Adhesion Molecules ◽

Surrounding Tissue ◽

Intercellular Adhesion Molecule ◽

Intercellular Adhesion Molecule 1 ◽

Endothelial Cell Surface

The emigration of leukocytes such as neutrophils into inflammatory sites requires adhesion to the endothelium of small venules. The initial adhesive event is margination characterized by rolling of neutrophils along the luminal surface of the endothelium. Each member of the selectin family of adhesion molecules has been shown to support neutrophil rolling under conditions of flow. E-selectin is synthesized by endothelial cells following cytokine stimulation, P-selectin is rapidly mobilized from Weibel–Palade bodies to the endothelial cell surface following stimulation with agents such as histamine, and L-selectin is constitutively expressed on the surface of leukocytes. Each selectin functions primarily as a lectin, recognizing carbohydrate structures on the leukocyte or endothelial cell surface. Once the marginated neutrophil forms a stationary adhesion with endothelial cells, it is stimulated by chemotactic factors to downregulate the selectin-based adhesion and upregulate adherence dependent on β2-integrins, principally CD11a/CD18 (LFA-1) and CD11b/CD18 (Mac-1). These adhesion molecules interact with intercellular adhesion molecule 1 (ICAM-1) and possibly other structures on the endothelial cell, and the leukocyte rapidly emigrates into surrounding tissue. Transendothelial migration in vitro is markedly inhibited by monoclonal antibodies against CD18 integrins or ICAM-1. Monoclonal antibodies against the selectins, CD18, CD11a, CD11b, and ICAM-1 have all been shown to significantly reduce the influx of neutrophils into sites of inflammation in various animal models.Key words: adhesion, integrins, selectins, leukocytes, endothelial cells.

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Alternatively activated macrophages actively inhibit proliferation of peripheral blood lymphocytes and CD4 + T cells in vitro

Immunology ◽

10.1046/j.1365-2567.1997.00371.x ◽

1997 ◽

Vol 92 (4) ◽

pp. 478-486 ◽

Cited By ~ 86

Author(s):

C. SCHEBESCH ◽

V. KODELJA ◽

C. MÜLLER ◽

N. HAKIJ ◽

S. BISSON ◽

...

Keyword(s):

T Cells ◽

Peripheral Blood ◽

Cd4 T Cells ◽

Peripheral Blood Lymphocytes ◽

Activated Macrophages ◽

Alternatively Activated Macrophages ◽

Blood Lymphocytes ◽

Alternatively Activated

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Expansion of a lymphocyte population co-expressing T4 (CD4) and T8 (CD8) antigens in the peripheral blood of a normal adult male

Blood ◽

10.1182/blood.v75.10.2024.bloodjournal75102024 ◽

1990 ◽

Vol 75 (10) ◽

pp. 2024-2029 ◽

Cited By ~ 1

Author(s):

NE Kay ◽

N Bone ◽

M Hupke ◽

AP Dalmasso

Keyword(s):

T Cells ◽

T Cell ◽

B Cell ◽

Adult Male ◽

Peripheral Blood ◽

Peripheral Blood Lymphocytes ◽

Normal Adult ◽

Cd8 Cells ◽

Blood Lymphocytes

Approximately 2% to 3% of circulating human T cells co-express CD4 and CD8 (CD4+, CD8+) T-cell antigens. These CD4+, CD8+ cells may be immature precursors that function to replenish functional T-cell subsets. We detected a very high level of CD4+, CD8+ cells in the peripheral blood lymphocytes of a healthy white male, ranging from 21% to 36%. The morphology of his peripheral blood lymphocytes was normal, and he has maintained an elevated level of CD4+, CD8+ cells without clinical disease over a 19-month observation period. The CD4+, CD8+ cells did not possess thymocyte membrane antigen (CD6), nor did they have increased Tac (CD25) antigen. His intact, purified blood T cells had a normal proliferative response to phytohemagglutinin and interleukin-2 (IL-2), provided help for B-cell proliferation at control levels and exposure to IL-2 resulted in generation of cytotoxic cells. However, the purified blood CD4+, CD8+ cells were deficient in these latter functions except for help in B-cell function. Despite defective function, the isolated CD4+, CD8+ cells co-expressed CD2 and CD3. Prolonged in vitro culture of CD4+, CD8+ cells was possible in the presence of recombinant IL-2. The cultured CD4+, CD8+ cells retained the double antigens (CD4 and CD8) throughout a 4-week period. It is likely these cells are less mature than CD4+, CD8- or CD4-, CD8+ T cells as the CD4+, CD8+ have less in vitro function than the former cells, but it is not yet clear if they mature into either CD4+, CD8-, or CD4-, CD8+ cells. Finally, the presence of an expanded, hypofunctioning CD4+, CD8+ cell population in a normal adult male is apparently compatible with excellent clinical health.

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In vitro expansion of CD4+CD25highFOXP3+CD127low/− regulatory T cells from peripheral blood lymphocytes of healthy Mycobacterium tuberculosis-infected humans

Microbes and Infection ◽

10.1016/j.micinf.2007.06.004 ◽

2007 ◽

Vol 9 (11) ◽

pp. 1325-1332 ◽

Cited By ~ 34

Author(s):

Jean-Michel Hougardy ◽

Virginie Verscheure ◽

Camille Locht ◽

Françoise Mascart

Keyword(s):

T Cells ◽

Mycobacterium Tuberculosis ◽

Regulatory T Cells ◽

Peripheral Blood ◽

Peripheral Blood Lymphocytes ◽

Blood Lymphocytes ◽

In Vitro Expansion

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Human monoclonal antibodies produced from L-leucine methyl ester-treated and in vitro immunized peripheral blood lymphocytes

Biochemical and Biophysical Research Communications ◽

10.1016/s0006-291x(87)80223-1 ◽

1987 ◽

Vol 148 (3) ◽

pp. 941-946 ◽

Cited By ~ 22

Author(s):

Carl A.K. Borrebaeek ◽

Lena Danielsson ◽

Susanna A. Möller

Keyword(s):

Monoclonal Antibodies ◽

Methyl Ester ◽

Peripheral Blood ◽

Peripheral Blood Lymphocytes ◽

Human Monoclonal Antibodies ◽

Blood Lymphocytes

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Expansion of a lymphocyte population co-expressing T4 (CD4) and T8 (CD8) antigens in the peripheral blood of a normal adult male

Blood ◽

10.1182/blood.v75.10.2024.2024 ◽

1990 ◽

Vol 75 (10) ◽

pp. 2024-2029 ◽

Cited By ~ 16

Author(s):

NE Kay ◽

N Bone ◽

M Hupke ◽

AP Dalmasso

Keyword(s):

T Cells ◽

T Cell ◽

B Cell ◽

Adult Male ◽

Peripheral Blood ◽

Peripheral Blood Lymphocytes ◽

Normal Adult ◽

Cd8 Cells ◽

Blood Lymphocytes

Abstract Approximately 2% to 3% of circulating human T cells co-express CD4 and CD8 (CD4+, CD8+) T-cell antigens. These CD4+, CD8+ cells may be immature precursors that function to replenish functional T-cell subsets. We detected a very high level of CD4+, CD8+ cells in the peripheral blood lymphocytes of a healthy white male, ranging from 21% to 36%. The morphology of his peripheral blood lymphocytes was normal, and he has maintained an elevated level of CD4+, CD8+ cells without clinical disease over a 19-month observation period. The CD4+, CD8+ cells did not possess thymocyte membrane antigen (CD6), nor did they have increased Tac (CD25) antigen. His intact, purified blood T cells had a normal proliferative response to phytohemagglutinin and interleukin-2 (IL-2), provided help for B-cell proliferation at control levels and exposure to IL-2 resulted in generation of cytotoxic cells. However, the purified blood CD4+, CD8+ cells were deficient in these latter functions except for help in B-cell function. Despite defective function, the isolated CD4+, CD8+ cells co-expressed CD2 and CD3. Prolonged in vitro culture of CD4+, CD8+ cells was possible in the presence of recombinant IL-2. The cultured CD4+, CD8+ cells retained the double antigens (CD4 and CD8) throughout a 4-week period. It is likely these cells are less mature than CD4+, CD8- or CD4-, CD8+ T cells as the CD4+, CD8+ have less in vitro function than the former cells, but it is not yet clear if they mature into either CD4+, CD8-, or CD4-, CD8+ cells. Finally, the presence of an expanded, hypofunctioning CD4+, CD8+ cell population in a normal adult male is apparently compatible with excellent clinical health.

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ИЗУЧЕНИЕ ВЛИЯНИЯ НАНОЧАСТИЦ СЕРЕБРА IN VITRO НА УРОВЕНЬ ЭКСПРЕССИИ МОЛЕКУЛЯРНЫХ МАРКЕРОВ АКТИВАЦИИ ЛИМФОЦИТОВ И МАРКЕРА АУТОИММУННОГО ПРОЦЕССА ПЕРИФЕРИЧЕСКОЙ КРОВИ БОЛЬНЫХ ВИРУСНОЙ ПАТОЛОГИЕЙ РОГОВИЦЫ

Biological Bulletin of Bogdan Chmelnitskiy Melitopol State Pedagogical University ◽

10.15421/2015013 ◽

2015 ◽

Vol 5 (02) ◽

pp. 8

Author(s):

V. A. Ulyanov ◽

L. N. Velichko ◽

A. V. Bogdanova ◽

M. B. Makarova

Keyword(s):

Monoclonal Antibodies ◽

Molecular Markers ◽

Peripheral Blood ◽

Phagocytic Activity ◽

Peripheral Blood Lymphocytes ◽

Lymphoid Cells ◽

Blood Lymphocytes ◽

Tissue Therapy ◽

Nanoparticles Of Silver

The influence of the nanoparticles of silver on the expression of molecular markers activation of lymphoid cells CD7+, CD25+, CD38+, CD45+, CD54+, CD95+, CD150+ and CD5+ – marker of the autoimmune process, as well as on phagocytic activity of neutrophils in patients with viral pathologies of the cornea was studied in vitro. In the Laboratory of Immunology, SI Institute of Eye Diseases and Tissue Therapy NAMS of Ukraine was developed technique of cultivation of peripheral blood lymphocytes with immunomodulation drugs, followed by determination of changes in the level of expression of molecular markers of lymphocyte activation. Assessment of the level of expression of molecular markers of activation of peripheral blood lymphocytes was performed method using a panel of monoclonal antibodies, CD5+, CD7+, CD25+, CD38+, CD45+, CD54+, CD95+ and CD 150+. The study was conducted in vitro with the peripheral lymphocytes the blood of 23 patients of viral pathology of the cornea. Our studies of the effects of nanosilver particles in vitro on the state of expression of molecular markers of activation of peripheral blood lymphocytes and phagocytic activity of neutrophils in patients with viral corneal pathology, showed a significant increase in the level of expression of the CD7+, CD25+, CD45+ and phagocytic activity of neutrophils after application silver nanoparticles. Key words: immune system, nanoparticles of silver, monoclonal antibodies, molecular markers activation.

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