Staphylococcus aureus biofilm properties and chronic rhinosinusitis severity scores correlate positively with total CD4+ T-cell frequencies and inversely with its Th1, Th17 and regulatory cell frequencies.

Chronic rhinosinusitis (CRS) represents chronic inflammation of the sinus mucosa characterised by dysfunction of the sinuses' natural defence mechanisms and induction of different inflammatory pathways ranging from a Th1 to a Th2 predominant polarisation. Recalcitrant CRS is associated with Staphylococcus aureus dominant mucosal biofilms; however, S. aureus colonisation of the sinonasal mucosa has also been observed in healthy individuals challenging the significance of S. aureus in CRS pathogenesis. We aimed to investigate the relationship between CRS key inflammatory markers, S. aureus biofilm properties/virulence genes and the severity of the disease. Tissue samples were collected during endoscopic sinus surgery from the ethmoid sinuses of CRS patients with (CRSwNP) and without (CRSsNP) nasal polyps and controls (n = 59). CD3+ T-cell subset frequencies and key inflammatory markers of CD4+ helper T cells were determined using FACS analysis. Sinonasal S. aureus clinical isolates were isolated (n = 26), sequenced and grown into biofilm in vitro, followed by determining their properties, including metabolic activity, biomass, colony-forming units and exoprotein production. Disease severity was assessed using Lund-Mackay radiologic scores, Lund-Kennedy endoscopic scores and SNOT22 quality of life scores. Our results showed that S. aureus biofilm properties and CRS severity scores correlated positively with total CD4+ T-cell frequencies but looking into CD4+ T-cell subsets showed an inverse correlation with Th1 and Th17 cell frequencies. CD4+ T-cell frequencies were higher in patients harbouring lukF.PV-positive S. aureus while its regulatory and Th17 cell subset frequencies were lower in patients carrying sea- and sarT/U-positive S. aureus. Recalcitrant CRS is characterised by increased S. aureus biofilm properties in relation to increased total CD4+ helper T-cell frequencies and reduced frequencies of its Th1, Th17 and regulatory T-cell subsets. These findings offer insights into the pathophysiology of CRS and could lead to the development of more targeted therapies.

Characteristics and postoperative dynamic changes in circulating CD4+ helper T lymphocytes in patients with breast cancer.

Introduction: Circulating CD4+ helper T cell (Th) subsets provide potentially important information on disease progression in several cancers. In this study, we explored the characteristics and postoperative dynamic changes in circulating CD4+Th subsets in patients with breast cancer. Methods: Circulating CD4+Th subsets, including CD4+ naive T cells (Tn), CD4+ central memory T cells (Tcm), CD4+ effector memory T cells (Tem), CD4+CD57+T, and CD4+PD-1+T, were detected with multiparameter flow cytometry. T-test and Wilcoxon rank-sum test were used to compare differences between groups for normally and non-normally distributed continuous variables, respectively. Postoperative dynamic changes in CD4+Th subsets were assessed using the paired-sample rank-sum test. Results: Seventy-five patients with invasive breast cancer and fifty-three patients with benign breast tumors were enrolled. Compared with that in patients with benign tumors, the proportion of CD4+Tn in patients with breast cancer patients decreased, whereas the proportion and absolute number of CD4+CD57+T and CD4+PD-1+T increased. Moreover, the proportion of CD4+PD-1+T was correlated with the clinicopathology of breast cancer. After tumor resection, the proportion and absolute number of CD4+Tcm significantly decreased, while those of CD4+Tem significantly increased, compared with preoperative values. Tumor resection caused significant changes in the proportion and absolute number of CD4+CD57+T and CD4+PD-1+ T, both of which showed significant decreases. Discussion: We found significant changes in circulating CD4+Th subsets in patients with breast cancer. Additionally, complete tumor resection can benefit the patient as it balances the patient's immunosuppression and immune stress and improves the immune exhaustion and immunosenescence states.

Th2 to Th1 Transition Is Required for Induction of Skin Lesions in an Inducible and Recurrent Murine Model of Cutaneous Lupus-Like Inflammation.

Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease characterized by a strong IFN signature, normally associated with type I IFNs. However, increasing evidence points to an additional role for IFNγ, or at least a pathogenic T effector subset dependent on IFNγ, for disease progression. Nevertheless, Th2 effector subsets have also been implicated in CLE. We have now assessed the role of specific T cell subsets in the initiation and persistence of skin disease using a T cell-inducible murine model of CLE, dependent on KJ1-26 T cell recognition of an ovalbumin fusion protein. We found that only Th2-skewed cells, and not Th1-skewed cells, induced the development of skin lesions. However, we provide strong evidence that the Th2 disease-initiating cells convert to a more Th1-like functional phenotype in vivo by the time the skin lesions are apparent. This phenotype is maintained and potentiates over time, as T cells isolated from the skin, following a second induction of self-antigen, expressed more IFN-γ than T cells isolated at the time of the initial response. Transcriptional analysis identified additional changes in the KJ1-26 T cells at four weeks post injection, with higher expression levels of interferon stimulated genes (ISGs) including CXCL9, IRF5, IFIH1, and MX1. Further, injection of IFN-γ-/- T cells faied to induce skin disease in mice. We concluded that Th2 cells trigger skin lesion formation in CLE, and these cells switch to a Th1-like phenotype in the context of a TLR7-driven immune environment that is stable within the T cell memory compartment.

Th9 Cell Differentiation and Its Dual Effects in Tumor Development.

With the improved understanding of the molecular pathogenesis and characteristics of cancers, the critical role of the immune system in preventing tumor development has been widely accepted. The understanding of the relationship between the immune system and cancer progression is constantly evolving, from the cancer immunosurveillance hypothesis to immunoediting theory and the delicate balance in the tumor microenvironment. Currently, immunotherapy is regarded as a promising strategy against cancers. Although adoptive cell therapy (ACT) has shown some exciting results regarding the rejection of tumors, the effect is not always satisfactory. Cellular therapy with CD4+ T cells remains to be further explored since the current ACT is mainly focused on CD8+ cytotoxic T lymphocytes (CTLs). Recently, Th9 cells, a subgroup of CD4+ T helper cells characterized by the secretion of IL-9 and IL-10, have been reported to be effective in the elimination of solid tumors and to exhibit superior antitumor properties to Th1 and Th17 cells. In this review, we summarize the most recent advances in the understanding of Th9 cell differentiation and the dual role, both anti-tumor and pro-tumor effects, of Th9 cells in tumor progression.

Roles for helper T cell lineage-specifying transcription factors in cellular specialization.

The development of specialized helper T cells has garnered much attention because of their critical role in coordinating the immune response to invading pathogens. Recent research emphasizing novel functions for specialized helper T cells in a variety of infectious disease settings, as well as autoimmune states, has reshaped our view on the capabilities of helper T cells. Notably, one previously underappreciated aspect of the lifespan of helper T cells is that they often retain the capacity to respond to changes in the environment by altering the composition of helper T cell lineage-specifying transcription factors they express, which, in turn, changes their phenotype. This emerging realization is changing our views on the stability versus flexibility of specialized helper T cell subtypes. Now, there is a new concerted effort to define the mechanistic events that contribute to the potential for flexibility in specialized helper T cell gene expression programs in the different environmental circumstances that allow for the re-expression of helper T cell lineage-specifying transcription factors. In addition, we are also now beginning to appreciate that "helper T cell" lineage-specifying transcription factors are expressed in diverse types of innate and adaptive immune cells and this may allow them to play roles in coordinating aspects of the immune response. Our current challenges include defining the conserved mechanisms that are utilized by these lineage-specifying transcription factors to coordinate gene expression programs in different settings as well as the mechanistic events that contribute to the differential downstream consequences that these factors mediate in unique cellular environments. In this review, we will explore our evolving views on these topics, often times using the Th1-lineage-specifying transcription factor T-bet as an example.