Human T cell activation by OKT3 is inhibited by a monoclonal antibody to CD44.

The CD44 molecule, also known as Hermes lymphocyte homing receptor, human Pgp-1, and extracellular matrix receptor III, has been shown to play a role in T cell adhesion and activation. Specifically, anti-CD44 mAb block binding of lymphocytes to high endothelial venules, inhibit T cell-E rosetting, and augment T cell proliferation induced by the CD2 or CD3-TCR pathways. We have characterized an anti-CD44 mAb (212.3) which immunoprecipitates a 90-kDa protein and is specific for CD44 as shown by peptide mapping and antibody competition studies. Interestingly, our studies with 212.3 demonstrate that this CD44-specific mAb completely inhibits T cell proliferation stimulated by the anti-CD3 mAb, OKT3. Inhibition is not a result of reduced cell viability, but is associated with 1) inhibition of IL-2 production, 2) inhibition of IL-2R expression, and 3) inhibition of OKT3-mediated increases in intracellular Ca2+ levels. In addition, 212.3 does not inhibit proliferation by the T cell mitogens PHA or PWM nor does it inhibit proliferation in a mixed lymphocyte reaction. Similar to other anti-CD44 mAb, 212.3 also augments T cell proliferation induced by mAb directed against the T11(2) and T11(3) epitopes of CD2. Thus, these studies describe a novel CD44-specific mAb (212.3) that inhibits T cell activation by OKT3 by blocking early signal transduction. Furthermore, these studies suggest that "receptor cross-talk" between the CD3-TCR complex and CD44 may regulate T cell activation.

CD44分子，也被称为赫耳墨斯淋巴细胞归巢受体、人类Pgp - 1以及细胞外基质受体III，已被证明在T细胞黏附和活化中发挥作用。具体而言，抗CD44单克隆抗体阻断淋巴细胞与高内皮微静脉的结合，抑制T细胞 - E花环形成，并增强由CD2或CD3 - TCR途径诱导的T细胞增殖。我们已经对一种抗CD44单克隆抗体（212.3）进行了特性分析，它能免疫沉淀一种90 kDa的蛋白质，并且通过肽图谱分析和抗体竞争研究表明其对CD44具有特异性。有趣的是，我们用212.3进行的研究表明，这种CD44特异性单克隆抗体完全抑制由抗CD3单克隆抗体OKT3刺激的T细胞增殖。这种抑制不是细胞活力降低的结果，而是与以下因素相关：1）抑制白细胞介素 - 2（IL - 2）的产生；2）抑制白细胞介素 - 2受体（IL - 2R）的表达；3）抑制OKT3介导的细胞内Ca²⁺水平的升高。此外，212.3不抑制T细胞有丝分裂原植物血凝素（PHA）或美洲商陆有丝分裂原（PWM）诱导的增殖，也不抑制混合淋巴细胞反应中的增殖。与其他抗CD44单克隆抗体类似，212.3也增强由针对CD2的T11(2)和T11(3)表位的单克隆抗体诱导的T细胞增殖。因此，这些研究描述了一种新型的CD44特异性单克隆抗体（212.3），它通过阻断早期信号转导来抑制OKT3对T细胞的激活。此外，这些研究表明CD3 - TCR复合物和CD44之间的“受体串扰”可能调节T细胞的激活。