Global Activation of CD8+ Cytotoxic T Lymphocytes Correlates with an Impairment in Regulatory T Cells in Patients with Generalized Vitiligo

Melanocyte-specific CD8+ cytotoxic T lymphocytes (CTLs) play a pivotal role in vitiligo-induced depigmentation. Yet, the mechanisms underlying the high frequency of generalized autoimmune disorders associated with generalized vitiligo (GV) are unknown. We hypothesized that an imbalance between activated CD8+ CTLs and regulatory T cells (Tregs) exists in patients with GV . Assessment of the circulating CD8+ CTLs and Tregs by flow cytometric analysis revealed an obvious expansion of CD8+ CTLs and a concomitant decrease in Treg cells in GV patients. The percentages of skin infiltrating CD8+ CTLs and Tregs were evaluated by immunohistochemistry and revealed dramatically increased numbers of both CD8+ CTLs and Tregs in the perilesional skin of GV patients. However, peripheral Tregs were impaired in their ability to suppress the proliferation and cytolytic capacity of autologous CD8+ T cells, suggesting that a functional failure of Tregs and the hyper-activation of CD8+ CTLs may contribute to progressive GV. Our data indicate that reduced numbers and impaired function of natural Tregs fail to control the widespread activation of CD8+ CTLs, which leads to the destruction of melanocytes and contributes to the elevated frequency of various associated autoimmune diseases. This knowledge furthers our understanding of the mechanisms of immune tolerance that are impaired in GV patients and may aid in the future development of effective immunotherapy for GV patients

Th17 Cells and Activated Dendritic Cells Are Increased in Vitiligo Lesions

Vitiligo is a common skin disorder, characterized by progressive skin de-pigmentation due to the loss of cutaneous melanocytes. The exact cause of melanocyte loss remains unclear, but a large number of observations have pointed to the important role of cellular immunity in vitiligo pathogenesis.In this study, we characterized T cell and inflammation-related dermal dendritic cell (DC) subsets in pigmented non-lesional, leading edge and depigmented lesional vitiligo skin. By immunohistochemistry staining, we observed enhanced populations of CD11c+ myeloid dermal DCs and CD207+ Langerhans cells in leading edge vitiligo biopsies. DC-LAMP+ and CD1c+ sub-populations of dermal DCs expanded significantly in leading edge and lesional vitiligo skin. We also detected elevated tissue mRNA levels of IL-17A in leading edge skin biopsies of vitiligo patients, as well as IL-17A positive T cells by immunohistochemistry and immunofluorescence. Langerhans cells with activated inflammasomes were also noted in lesional vitiligo skin, along with increased IL-1ß mRNA, which suggest the potential of Langerhans cells to drive Th17 activation in vitiligo.These studies provided direct tissue evidence that implicates active Th17 cells in vitiligo skin lesions. We characterized new cellular immune elements, in the active margins of vitiligo lesions (e.g. populations of epidermal and dermal dendritic cells subsets), which could potentially drive the inflammatory responses

Wpływ temperamentu i szybkości doju na długość użytkowania, wydajność życiową i przyczyny brakowania krów

Influence of cow temperament and milking speed on herd life, lifetime milk yield and reasons of cow culling.Importance of functional traits, longevity or reproduction traits increases continuously in present dairy cattle breeding. Effects of milking speed and cow temperament on herd life, lifetime milk yield and reasons of culling were estimated. The highest lifetime yield (p<0.01) of milk, fat and protein as well as life span and herd life had calm animals or slow milking cows. However, cows with normal temperament or fast milking had the highest (p<0.01) yield of milk fat and protein per one day of utilization. The main reason of culling were fertility and reproductive disorders (on average 41.2%), but 15.3% cows were culled because of udder diseases. Results suggest highly significant (p<0.01) influence of temperament and milking speed on life span, herd life, lifetime milk yield. Functional traits, longevity or fertility should be parts of breeding programs to balance dairy cattle selection and compensate negative influence of selection only towards milk yield that took place in the past.Wpływ temperamentu i szybkości doju na długość użytkowania, wydajność życiową i przyczyny brakowania krów. Cechy związane z użytkowością, długowiecznością czy rozrodem bydła mlecznego mają coraz większe znaczenie w tworzeniu programów hodowlanych. Oceniono wpływ szybkości doju (bardzo wolne, wolne, przeciętnie, szybko, bardzo szybko) i temperamentu krów (zwierzę powolne, normalnie reagujące, pobudliwe lub agresywne) na długość ich użytkowania, życiową wydajność oraz przyczyny brakowania. Najwyższą wydajnością (p<0,01) życiową mleka, tłuszczu i białka oraz długością życia i użytkowania cechowały się zwierzęta powolne lub te wolno oddające mleko. Jednak to krowy normalnie reagujące lub o szybkim tempie oddawania mleka miały najwyższą (p<0,01) wydajność mleka, tłuszczu i białka na jeden dzień użytkowania. Główną przyczyną brakowania krów była jałowość i choroby układu rozrodczego (średnio 41,2%), jednak 15,3% wszystkich krów wybrakowano z powodu chorób wymienia. Otrzymane wyniki sugerują istotny (p<0,01) wpływ temperamentu oraz szybkości doju na długość życia i użytkowania krów oraz ich wydajność życiową. Cechy użytkowe, długowieczność czy płodność powinny być wykorzystane do tworzenia indeksów selekcyjnych, by zrównoważyć negatywny wpływ selekcji skoncentrowanej w przeszłości głównie na zwiększaniu wydajności mlecznej

Measuring of quality of life in autoimmune blistering disorders in Poland. Validation of disease – specific Autoimmune Bullous Disease Quality of Life (ABQOL) and the Treatment Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaires

© 2016 Medical University of Bialystok Purpose Autoimmune bullous dermatoses (AIBD) are rare, severe diseases resulting from some antibodies activity against the different adhesion structures within the skin and/or mucosa. Few studies investigated quality of life (QOL) in AIBD by generic and dermatology-specific instruments, all reporting strong impact on QOL. Recently, disease-specific measurement tools have been developed: Autoimmune Bullous Disease Quality of Life (ABQOL) and Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaires. The aim of this study was to test the reliability and validity of ABQOL and TABQOL by developing the first foreign language versions and to evaluate ABQOL and TABQOL in Polish patients. Material and methods The study enrolled 80 patients from the tertiary referral center for AIBD at the outpatient clinic or on admission to the hospital. Sixty six patients completed the 17-item questionnaires of each ABQOL and TABQOL at day 0 and after 5–7 days. Both questionnaires were translated into Polish according to protocol. Results The internal consistency and test–retest reliability were high (Cronbach α = 0.95 for ABQOL, α = 0.87 for TABQOL), (R = 0.98 for ABQOL, R = 0.86 for TABQOL). In convergent validity, the correlation of ABQOL and TABQOL was strong (R = 0.81), but low with objective disease activity scales. The strongest impact of AIBD on QOL has been observed in flares and in patients with the onset below 70 years of age. The patients with bullous pemphigoid had the highest QOL compared to other AIBD patients. Conclusions The ABQOL and TABQOL are reliable and valid instruments for the assessment of QOL in AIBD