Superantigens and Chronic Rhinosinusitis: Skewing of T-Cell Receptor Vβ-Distributions in Polyp-Derived CD4⁺and CD8⁺T Cells

Abstract

This study establishes evidence of S. aureus SAg-T-cell interactions in polyp lymphocytes of 35% of CRSwNP patients. Although these results are consistent with intranasal exposure of polyp lymphocytes to SAg's, additional study is necessary to establish the role of these toxins in disease pathogenesis.

The structure of superantigen complexed with TCR and MHC reveals novel insights into superantigenic T cell activation

“…In addition to the important information regarding the nature of such a potent T cell stimulus as SAgs, the finding presented here have vital implications for future strategies in designing drugs aimed to prevent or interfere with the interactions between SAgs and the host receptors. One important consequence is that investigating whether a patient has a skewed variable β-domain repertoire, which is a common way to determine whether a disease is caused by SAg or not [32][33][34] , may be misleading, as our results show that Vβ interaction is not the exclusive means of T cell activation by SAgs. Thus, the results presented here, describing the previously unknown feature of SAgs, activation of T cells through the TCRVα, could have significance for the understanding of these diseases.…”

Efficient characterization of the TCR repertoire in lymph nodes by flow cytometry

“…However, it is well known that circulating lymphocytes do not exactly reflect the situation in tissues where pathologic lesions occur (6,17,23,33,37). Of note, investigations in sites other than peripheral blood have infrequently been conducted using flow cytometry (13,17,20,21,24,(32)(33)(34). As regards lymph nodes, only six studies primarily addressed this question, and these included few patients or used few anti-Vb mAbs (13,23,34,(36)(37)(38).…”

“…The TCR repertoire has been frequently studied in various diseases, but mainly in blood samples (6,14,15,19,(21)(22)(23)37,39), and more rarely in injured organs (3)(4)(5)(6)(7)(8)(9)(10)17,20,21,24,(32)(33)(34). However, it is well known that circulating lymphocytes do not exactly reflect the situation in tissues where pathologic lesions occur (6,17,23,33,37).…”

“…Such an approach by flow cytometry proved to be efficient in detecting skewing of the TCR-repertoire in blood samples. Indeed, oligoclonal expansions or restrictions of some families have been demonstrated in allergy (14), autoimmune disease (15)(16)(17)(18)(19), infection (20)(21)(22)(23), cancer (24,25), and immunodeficiency (26,27). In addition, homogeneous expansions have been characterized in T-cell lymphoproliferative disorders (11,(28)(29)(30)(31).…”

Chronic sinusitis pathophysiology: The role of allergy

“…8,45 These bacteria can drive the recurrent acute infections that plague CS patients, when they transform into their planktonic state and emerge from the biofilm. However, even in their indolent biofilm-associated state, these bacteria are not innocuous and can be a robust source of superantigens, [45][46][47][48][49] immune adjuvants, and of allergenic (IgE inducing) proteins (Fig. 2).…”