CD4+ T Cell and Eosinophil Adhesion Is Mediated by Specific ICAM-3 Ligation and Results in Eosinophil Activation

Abstract

T cells and eosinophils, which are found in close proximity in asthmatic lungs, express many surface receptors that are counterligands. These data suggest that direct interactions between these cell types could play an important role in regulating airway inflammation in asthma. We examined the effect of selective adhesion between counterligands on human eosinophils and CD4+ T cells to determine 1) the existence of specific adhesive interactions and 2) if augmented specific adhesion to CD4+ T cells also caused augmented secretion of leukotriene C4 (LTC4) from eosinophils. A new method for binding of human CD4+ T cells to microwell plates was developed, which allowed for specific quantitative assessment of eosinophil adhesion to individual CD4+ T cells in culture. Adhesion of CD4+ T cells to eosinophils was minimal in unstimulated cells but increased after activation of T cells by PMA. Augmented adhesion was regulated substantially through binding of ICAM-3 and only minimally by ICAM-1. We further evaluated whether this specific adhesion up-regulated stimulated secretion of LTC4 from eosinophils. Adhesion with CD4+ T cells augmented eosinophil secretion of LTC4 caused by FMLP plus cytochalasin. Blockade of ICAM-3, as well as ICAM-1, inhibited completely the augmented secretion of eosinophil LTC4. We demonstrate that eosinophils and CD4+ T cells are capable of ligand-specific adhesion that is mediated predominantly by ICAM-3 ligation and that this binding causes augmented eosinophil secretion.

CD4+ T cells enhance the unloaded shortening velocity of airway smooth muscle by altering the contractile protein expression

“…A direct interaction between activated human CD4 + T cells and eosinophils occurs through the intercellular cell adhesion molecule 3 receptor (Douglas et al . ). Moreover, cytokines released by human CD4 + T cells regulate the priming, activation and survival of eosinophils (Rothenberg et al .…”

Intrinsic AHR in IL-5 transgenic mice is dependent on CD4+cells and CD49d-mediated signaling

“…ϩ T cells use CAMs to bind eosinophils, inducing activation of these cells as determined by leukotriene production (5). Regardless of the specific mechanism utilized by T and/or CD4 ϩ cells, the dependence of the intrinsic AHR associated with naive NJ.1726 mice suggests that potential direct IL-5 agonist activities on airway smooth muscle alone are not sufficient to elicit AHR.…”

“…Several eosinophil-dependent mechanisms that contribute and/or cause pulmonary pathology and airway dysfunction have been suggested, including the release of lipid mediators, granule proteins, and reactive oxygen species (9). Eosinophil activation has been demonstrated in vitro by a number of mechanisms such as ␣ 4 -integrin (CD49d)-dependent binding to extracellular matrix fibronectin (29,26), eosinophil adhesion to CD4 ϩ T cells (5), response to CD3-stimulated Th2 cell supernatants (28), and eotaxin binding to CCR3 chemokine receptors (19). These data demonstrate that multiple and complex interactions between the eosinophil and the pulmonary microenvironment may be required for cell activation and the development of AHR.…”

Allergy and sports

“…Generally, it is divided into “allergic” (or extrinsic) and “nonallergic” (or intrinsic) (36). The accumulation of eosinophils in the airways, the production of various proinflammatory cytokines leading to the activation of endothelial cells inducing, in turn, adhesion molecules such as ICAM‐1, ICAM‐2, and ICAM‐3 (37), VCAM‐1, selectins, and RANTES, leads to a complex inflammatory process which ends with several clinical expressions that depend both on the various stimuli and on individual responses based, for asthmatic subjects, mainly on atopy (38–45).…”