María Luisa Pita-López

Effect of ageing on CMV-specific CD8 T cells from CMV seropositive healthy donors

BackgroundAgeing is associated with changes in the immune system with substantial alterations in T-lymphocyte subsets. Cytomegalovirus (CMV) is one of the factors that affect functionality of T cells and the differentiation and large expansions of CMV pp65-specific T cells have been associated with impaired responses to other immune challenges. Moreover, the presence of clonal expansions of CMV-specific T cells may shrink the available repertoire for other antigens and contribute to the increased incidence of infectious diseases in the elderly. In this study, we analyse the effect of ageing on the phenotype and frequency of CMV pp65-specific CD8 T cell subsets according to the expression of CCR7, CD45RA, CD27, CD28, CD244 and CD85j.ResultsPeripheral blood from HLA-A2 healthy young, middle-aged and elderly donors was analysed by multiparametric flow cytometry using the HLA-A*0201/CMV pp65495–504 (NLVPMVATV) pentamer and mAbs specific for the molecules analysed. The frequency of CMV pp65-specific CD8 T cells was increased in the elderly compared with young and middle-aged donors. The proportion of naïve cells was reduced in the elderly, whereas an age-associated increase of the CCR7null effector-memory subset, in particular those with a CD45RAdim phenotype, was observed, both in the pentamer-positive and pentamer-negative CD8 T cells. The results also showed that most CMV pp65-specific CD8 T cells in elderly individuals were CD27/CD28 negative and expressed CD85j and CD244.ConclusionThe finding that the phenotype of CMV pp65-specific CD8 T cells in elderly individuals is similar to the predominant phenotype of CD8 T cells as a whole, suggests that CMV persistent infections contributes to the age-related changes observed in the CD8 T cell compartment, and that chronic stimulation by other persistent antigens also play a role in T cell immunosenescence. Differences in subset distribution in elderly individuals showing a decrease in naive and an increase in effector-memory CD8 T cells may be relevant in the age-associated defective immune response.

Adaptive Memory of Human NK-like CD8+ T-Cells to Aging, and Viral and Tumor Antigens

Human natural killer (NK)-like CD8+ T-cells are singular T-cells that express both T and NK cell markers such as CD56; their frequencies depend on their differentiation and activation during their lifetime. There is evidence of the presence of these innate CD8+ T-cells in the human umbilical cord, highlighting the necessity of investigating whether the NK-like CD8+ T-cells arise in the early stages of life (gestation). Based on the presence of cell surface markers, these cells have also been referred to as CD8+KIR+ T-cells, innate CD8+ T-cells, CD8+CD28−KIR+ T-cells or NKT-like CD8+CD56+ cells. However, the functional and co-signaling significance of these NK cell receptors on NK-like CD8+ T-cells is less clear. Also, the diverse array of costimulatory and co-inhibitory receptors are spatially and temporally regulated and may have distinct overlapping functions on NK-like CD8+ T-cell priming, activation, differentiation, and memory responses associated with different cell phenotypes. Currently, there is no consensus regarding the functional properties and phenotypic characterization of human NK-like CD8+ T-cells. Environmental factors, such as aging, autoimmunity, inflammation, viral antigen re-exposure, or the presence of persistent tumor antigens have been shown to allow differentiation (“adaptation”) of the NK-like CD8+ T-cells; the elucidation of this differentiation process and a greater understanding of the characteristics of these cells could be important for their eventual in potential therapeutic applications aimed at improving protective immunity. This review will attempt to elucidate an understanding of the characteristics of these cells with the goal toward their eventual use in potential therapeutic applications aimed at improving protective immunity.

CD28-, CD45RAnull/dim and natural killer-like CD8+ T cells are increased in peripheral blood of women with low-grade cervical lesions

BackgroundIn response to antigen naive CD8+, T cells differentiate into effector cells, which express Natural killer (NK) receptors, lose CD28 expression, and die by apoptosis. However, in smaller quantities, the cells are retained for subsequent exposure to the same antigen. Knowledge is limited regarding whether the percentages of CD28-, Effector memory (EMRAnull/dim), and the CD16+/CD56 + CD8+ T cells of women with low-grade cervical lesions are altered at a systemic level.MethodsWe enrolled in this study women controls and women with Human papilloma virus infection (HPV-I) without associated cellular neoplastic changes and with Cervical Intraepithelial Neoplastic-I (CIN-I). Flow cytometry (FC) was performed for measurement of CD28-, memory subset, and NK-like CD8 + T cells, and IL-17, IFN-gamma, Tumor necrosis factor (TNF)-alpha, Interleukin (IL)-10, IL-6, IL-4, and IL-2. Finally, we genotyped the HPV.ResultsThe CIN-I group increased the CD8 + CD28− and CD16+/56+ T cell percentage compared with that of HPV-I and controls (p <0.01), and CD8 + CCR7-CD45RAnull/dim (EMRAnull/dim) T cells were also increased in the CIN-I group compared with the controls (p <0.01). These two study groups were HPV- genotyped; 49% were HPV18+, and we did not observe differences in cytokine levels among all groups.ConclusionsIncreased levels of CD28-, EMRAnull/dim, and CD16+/CD56 + CD8+ T cells of peripheral blood in women with CIN-I may be associated with persistent HPV infection and could exert an influence on progression to cervical cancer.

INDICADORES DE ESTRÉS OXIDATIVO EN SUERO Y COMPORTAMIENTO ALIMENTARIO EN ADULTOS DE UNA ZONA RURAL DE JALISCO, MÉXICO

INTRODUCTION The feeding behavior establishes a relation of humans with food, includes food habits that could be involved with oxidative stress. OBJECTIVE To evaluate the relation of indicators of oxidative stress (lipid peroxides) and antioxidant (ascorbic acid, catalase, superoxide dismutase) with feeding behavior in adults of Teocuhitatlan Corona, Jalisco, Mexico. METHOD Study observational, descriptive, cross-sectional of 44 adults with 43 to 88 years, was used a instrument of feeding behavior. The questionnaire were related to indicators of oxidative stress. Were used descriptive statistics, frequency distribution and analysis of covariance with adjustment variables, was considered significant p <0.05. RESULTS The values of serum lipid peroxides were related to behaviors: consider the nutritional content as most important when choosing food (p = 0.042), dislike milk (p = 0.027), intake of sweets between meals (p = 0.001), habitual inclusion of vegetables and salads in main meal (p = 0.018). We do not found association in to values of ascorbic acid, cholesterol in low density lipoproteins and enzymatic activities of catalase and superoxide dismutase with food behaviors. DISCUSSION The feeding behaviors analyzed in this study may be involved with development of oxidative stress and could be have protective or harmful effect in development to complications of chronic non-communicable diseases and aging in this population. This suggests to analyze demographic and socio-cultural aspects of region and besides analyzing the consumption and metabolic markers related to food.