Expression, epitope analysis, and functional role of the LFA-2 antigen detectable on neoplastic mast cells

Author:

Schernthaner Gerit-Holger1,Jordan John-Hendrik1,Ghannadan Minoo1,Agis Hermine1,Bevec Dorian1,Nuñez Rosa1,Escribano Luis1,Majdic Otto1,Willheim Martin1,Worda Christof1,Printz Dieter1,Fritsch Gerhard1,Lechner Klaus1,Valent Peter1

Affiliation:

1. From the Department of Internal Medicine I, Division of Hematology & Hemostaseology, Institute of Immunology, Institute of Pathophysiology, Department of Obstetrics and Gynecology, Division of Gynecological Endocrinology and Reproductive Medicine, University of Vienna, Austria; Axxima Pharmaceuticals, Martinsried, Germany; Servicio de Hematologia, Mast Cell Unit, Hospital Ramón y Cajal, University of Alcalá de Henares, Madrid, Spain; and St Anna Children's Hospital, Vienna, Austria.

Abstract

AbstractRecent data suggest that mast cells (MCs) in patients with systemic mastocytosis or mast cell leukemia express a CD2-reactive antigen. To explore the biochemical nature and function of this antigen, primary MCs as well as the MC line HMC-1 derived from a patient with mast cell leukemia were examined. Northern blot experiments revealed expression of CD2 messenger RNA in HMC-1, whereas primary nonneoplastic MCs did not express transcripts for CD2. In cell surface staining experiments, bone marrow (BM) MCs in systemic mastocytosis (n = 12) as well as HMC-1 cells (30%-80%) were found to express the T11-1 and T11-2 (but not T11-3) epitopes of CD2. By contrast, BM MCs in myelodysplastic syndromes and nonhematologic disorders (bronchiogenic carcinoma, foreskin phimosis, uterine myeomata ) were consistently CD2−. All MC species analyzed including HMC-1 were found to express LFA-3 (CD58), the natural ligand of CD2. To study the functional role of CD2 on neoplastic MCs, CD2+ and CD2− HMC-1 cells were separated by cell sorting. CD2+ HMC-1 cells were found to form spontaneous aggregates and rosettes with sheep erythrocytes in excess over CD2−cells, and a T11-1 antibody inhibited both the aggregation and rosette formation. Moreover, exposure of CD2+ HMC-1 cells to T11-1 or T11-2 antibody was followed by expression of T11-3. In addition, stimulation of neoplastic MCs through T11-3 and a second CD2 epitope resulted in histamine release. These data show that neoplastic MCs express functionally active CD2. It is hypothesized that expression of CD2 is associated with pathologic accumulation and function of MCs in systemic mastocytosis.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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