Regulatory T-Cell Distribution within Lung Compartments in COPD

Abstract

The importance of the adaptive immune response, specifically the role of regulatory T (Treg) cells in controlling the obstruction progression in smokers, has been highlighted. To quantify the adaptive immune cells in different lung compartments, we used lung tissues from 21 never-smokers without lung disease, 22 current and/or ex-smokers without lung disease (NOS) and 13 current and/or ex-smokers with chronic obstructive pulmonary disease (COPD) for histological analysis. We observed increased T, B, IL-17 and BAFF cells in small and large airways of COPD individuals; however, in the NOS, we only observed increase in T and IL-17 cells only in small airways. A decrease in the density of Treg, TGF-β and IL-10 in small and large airways was observed only in COPD individuals. In the lymphoid tissues, Treg, T,B-cells and BAFF cells were also increased in COPD; however, changes in Treg inhibitory associated cytokines were not observed in this compartment. Therefore, our results suggest that difference in Treg cell distributions in lung compartments and the decrease in TGF-β and IL-10 cells in the airways may lead to the obstruction in smokers.

Levels of CD4+ CD25+ T Regulatory Cells in Bronchial Mucosa and Peripheral Blood of Chronic Obstructive Pulmonary Disease Indicate Involvement of Autoimmunity Mechanisms

“…There is a debate over Treg numbers in COPD tissue. According to other studies, the number of CD4+ CD25+ FOXP3 Tregs in the bronchial biopsies [22] or lungs [23,24] of patients with stable COPD is not significantly different compared with healthy controls but is decreased in the small airways of COPD patients, and this negatively correlates with the degree of airflow obstruction [11,25]. However, in our study we found significantly lower numbers of intraepithelial CD4+ CD25+ lymphocytes in the severe/very severe COPD (GOLD III-IV) group as well as in the control non-smokers group, compared with mild/moderate COPD and control smokers groups.…”

Sputum from chronic obstructive pulmonary disease patients inhibits T cell migration in a microfluidic device

“…Another study showed comparable percentages of CD8 + T cells in the airway among all the study groups, including healthy nonsmokers, asymptomatic smokers, and male COPD patients . Viral infections that commonly occur in COPD patients, such as by adenovirus or rhinovirus, may lead to foreign antigenic stimulus followed by CD8 + T cell response as a secondary antivirus function . In this model, the innate immune response triggers the maturation and migration of dendritic cells (DCs) to the paratracheal lymph nodes, wherein T cells, especially CD8 + T cells, are activated and expanded .…”

“…34 Viral infections that commonly occur in COPD patients, such as by adenovirus or rhinovirus, may lead to foreign antigenic stimulus followed by CD8 + T cell response as a secondary antivirus function. [35][36][37][38][39] In this model, the innate immune response triggers the maturation and migration of dendritic cells (DCs) to the paratracheal lymph nodes, wherein T cells, especially CD8 + T cells, are activated and expanded. 39,40 While DCs in COPD patients failed to appropriately guide T cell responses, it resulted in a diffusive distribution of the expanded CD8 + T cells into the lung in a chronic inflammatory progression.…”

“…[35][36][37][38][39] In this model, the innate immune response triggers the maturation and migration of dendritic cells (DCs) to the paratracheal lymph nodes, wherein T cells, especially CD8 + T cells, are activated and expanded. 39,40 While DCs in COPD patients failed to appropriately guide T cell responses, it resulted in a diffusive distribution of the expanded CD8 + T cells into the lung in a chronic inflammatory progression. 39,41,42 Thus, the increased appearance of T cells, particularly the predominant CD8 + T cells, in the airways in COPD may be due to its de novo origin or diffusive distribution rather than chemotaxis-based recruitment from blood in response to airway secreted chemotactic factors.…”

“…39,40 While DCs in COPD patients failed to appropriately guide T cell responses, it resulted in a diffusive distribution of the expanded CD8 + T cells into the lung in a chronic inflammatory progression. 39,41,42 Thus, the increased appearance of T cells, particularly the predominant CD8 + T cells, in the airways in COPD may be due to its de novo origin or diffusive distribution rather than chemotaxis-based recruitment from blood in response to airway secreted chemotactic factors. In this context, the observed inhibitory effect of COPD sputum in our study may suggest a stop signal for the infiltrated T cells to accumulate in the lung, which facilitates the pathogenesis of COPD.…”