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Background: Although exposure to stings has been identified as the leading risk factor for anaphylaxis due to Hymenoptera venom allergy, professional beekeepers receive hundreds of stings yearly without developing systemic reactions. Objective: This study aims to analyze the mechanisms underlying bee venom tolerance in beekeepers. Methods: A cross-sectional study was conducted. Participants were recruited and classified into 3 groups: allergic patients (APs), who experienced systemic reactions after bee stings, with a positive intradermal test and specific IgE (sIgE) to Apis mellifera venom (AmV); tolerant beekeepers (TBKs), who received ≥50 stings/year; and healthy nonexposed controls (HCs). We measured serum levels of sIgE and specific IgG4 (sIgG4) to AmV, rApi m 1, rApi m 2, rApi m 3, Api m 4, rApi m 5, and rApi m10, as well as AmV-induced basophil degranulation, percentage of T-cell subsets, regulatory T cells (Treg), and IL-10 production. Results: Compared with TBKs, APs had high levels of sIgE to AmV and all its allergic components (P

Este artículo propone una lectura para todos los glifos incertos en las imágenes que acom-pañan el capítulo 21 del libro IX del Códice Florentino, siguiendo el trabajo de desciframiento iniciado por Frances Berdan (2015). Estas imágenes representan el proceso de trabajo de plumaria a principios del período colonial, expresando los nombres de los materiales uti-lizados por los artistas de la pluma o amanteca, sus propiedades, así como las acciones implicadas en la fabricación de sus obras de arte. El análisis de estos glifos demuestra que constituyen una especie de “manual de instrucciones”, y posiblemente una de las formas de transmisión del arte y la artesanía entre los indígenas de México durante el siglo XVI, época de fuerte transculturación. El análisis también revela cómo los enfoques estrictamente fonocéntricos de la gramatología son insuficientes para abordar la complejidad de la escritura azteca y para comprender sus posibilidades comunicativas. En su lugar, proponemos que en estas páginas, las imágenes funcionan junto con los glifos logosilábicos, codificando ‘textos incorporados’, como los define Janet Berlo (1983), textos que tenían cierto grado de indepen-dencia de los escritos en español e incluso de los en náhuatl alfabético, por lo que pueden considerarse como verdaderas pictografías, textos indígenas con el potencial de descolonizar nuestra idea de escritura., Miradas - Revista de Historia del Arte y la Cultura de las Américas y la Península Ibérica, Bd. 7 (2023): Miradas

This article proposes a reading for all the glyphs infixed in the images which accompany the twenty-first chapter of Book 9 of the Florentine Codex, following the decipherment work initiated by Frances Berdan (2015). These images depict the process of featherworking during the early colonial period, expressing the names of the materials used by the feather artists or amanteca, their properties, as well as the actions involved in the manufacture of their artworks. The analysis of these glyphs shows that they constitute a sort of technical ‘instruction manual’, and possibly corresponded to one of the ways in which arts and crafts were transmitted among the indigenous people of Mexico during the sixteenth century, an era of strong transculturation. The analysis also reveals how strict phonocentric approaches in grammatology are insufficient to tackle the complexity of Aztec writing and to understand its communicative possibilities. Instead, we propose that, in these pages, images work together with logosyllabic glyphs, codifying ‘embedded texts’, as defined by Janet Berlo (1983), texts which had a degree of independence from those written in Spanish and even alphabetic Nahuatl, and hence can be considered as true pictographies, indigenous texts with the potential to decolonise our idea of writing., Miradas - Journal for the Arts and Culture of the Américas and the Iberian Peninsula, Bd. 7 (2023): Miradas

A better understanding of the complex interactions between the immune system and tumour cells from different origins has opened the possibility to design novel procedures of antitumoral immunotherapy. One of these novel approaches is based on the use of autologous or allogeneic natural killer (NK) cells to treat cancer. In the last decade, different strategies to activate NK cells and their use in adoptive NK cell-based therapy have been established. Although NK cells are often considered as a uniform cell population, several phenotypic and functionally distinct NK cells subsets exist in healthy individuals, that are differentially affected by ageing or by apparently innocuous viruses such as cytomegalovirus (CMV). In addition, further alterations in the expression of activating and inhibitory receptors are found in NK cells from cancer patients, likely because of their interaction with tumour cells. Thus, NK cells represent a promising strategy for adoptive immunotherapy of cancer already tested in phase 1/2 clinical trials. However, the existence of NK cell subpopulations expressing different patterns of activating and inhibitory receptors and different functional capacities, that can be found to be altered not only in cancer patients but also in healthy individuals stratified by age or CMV infection, makes necessary a personalized definition of the procedures used in the selection, expansion, and activation of the relevant NK cell subsets to be successfully used in NK cell-based immunotherapy.

Immunosenescence affects innate and adaptive immunity impairing the response to pathogens and vaccines. Chronic infection with cytomegalovirus (CMV) has been shown to drive “early immunosenescence” and can considerably affect both the function and phenotype of immune cells, especially T cells. We have previously shown that the expression of CD57, CD300a, and CD161 was differentially affected by age and chronic CMV infection, indicating that these markers are a hallmark of CMV infection and T-cell aging. The aim of this present study was to clarify whether these 3 markers define distinct T-cell subpopulations with a specific functional and molecular signature. Specifically, we analyzed the effect of age and chronic CMV infection on the functionality of T cells according to CD161, CD300a, and CD57 expression. We found that these markers defined different T-cell subsets, both at the phenotypic and functional levels. CD57 was the best biomarker for CD4+ T-cell cytotoxicity and was a hallmark of CMV infection. CD300a+ T cells were heterogeneous and included different cell subsets. The population of CD161+ T cells dramatically decreased with age, independently of CMV infection, and represented a sign of age-associated immune system alterations. The latter could contribute to an increased risk of autoimmune disease and infection in older adults. Our results underline the importance of better understanding the factors involved in the immunosenescence process to be able to uncover new biomarkers and open new avenues for the investigation and development of novel age-related disease therapies.

Background: Acute myeloid leukemia (AML) remains a major clinical challenge due to poor overall survival, which is even more dramatic in elderly patients. TIGIT, an inhibitory receptor that interacts with CD155 and CD112 molecules, is considered as a checkpoint in T and NK cell activation. This receptor shares ligands with the co-stimulatory receptor DNAM-1 and with TACTILE. The aim of this work was to analyze the expression of DNAM-1, TIGIT and TACTILE in NK cells and T cell subsets in AML patients. Methods: We have studied 36 patients at the time of diagnosis of AML and 20 healthy volunteers. The expression of DNAM-1, TIGIT and TACTILE in NK cells and T cells, according to the expression of CD3 and CD56, was performed by flow cytometry. Results: NK cells, CD56&minus, T cells and CD56+ T (NKT-like) cells from AML patients presented a reduced expression of DNAM-1 compared with healthy volunteers. An increased expression of TIGIT was observed in mainstream CD56&minus, T cells. No differences were observed in the expression of TACTILE. Simplified presentation of incredibly complex evaluations (SPICE) analysis of the co-expression of DNAM-1, TIGIT and TACTILE showed an increase in NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE. Low percentages of DNAM-1&minus, TIGIT+TACTILE+ NK cells and DNAM-1&minus, TIGIT+TACTILE+ CD56&minus, T cells were associated with a better survival of AML patients. Conclusions: The expression of DNAM-1 is reduced in NK cells and in CD4+ and CD8+ T cells from AML patients compared with those from healthy volunteers. An increased percentage of NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE is associated with patient survival, supporting the role of TIGIT as a novel candidate for checkpoint blockade.

Background Acute kidney injury (AKI) occurs in 12–20% of multiple myeloma (MM) patients. Several studies have shown a reduction of free light chains (FLC) using hemodialysis with High-Cut-Off membranes. However, this technique entails albumin loss. Hemodiafiltration with ultrafiltrate regeneration is a technique that includes a process of adsorption. The aim of this study was to evaluate the effectiveness of hemodiafiltration with ultrafiltrate regeneration in reducing FLC levels without causing albumin loss. Methods This is an observational study (2012 to 2018) including nine patients with MM (5 kappa, 4 lambda) and AKI. All patients were treated with chemotherapy and hemodiafiltration with ultrafiltrate regeneration. Blood Samples (pre and post-dialysis) and ultrafiltrate were collected pre and post-resin at 5 min after initiation of the session and 5 min before the end of the procedure. Results The serum levels of kappa and lambda were reduced by a 57.6 ± 10% and 33.5 ± 25% respectively. Serum albumin concentration remained unchanged after the procedure. In the ultrafiltrate, the mean FLC reduction ratio shortly after initiation of the dialysis procedure was: 99.2 and 97.06% for kappa and lambda respectively, and only 0.7% for albumin; and at the end of the session the percent reduction was: 63.7 and 33.62% for kappa and lambda respectively, and 0.015% for albumin. Patients clinical outcome was: 33.3% recovered renal function, 22.2% died during the first year and 44.4% required maintenance dialysis. Conclusions Hemodiafiltration with ultrafiltrate regeneration reduces FLC levels without producing a significant loss of albumin; and, FLC removal is maintained throughout the session. Therefore, hemodiafiltration with ultrafiltrate regeneration may be considered an effective adjunctive therapy in patients with MM.

Resumen Antecedentes y objetivo La determinacion de inmunoglobulinas en suero y, concretamente de IgG y de subclases de IgG, es fundamental para el diagnostico clinico de numerosas patologias. Los metodos de deteccion habituales proporcionan resultados diferentes segun el analizador utilizado. El objetivo de este estudio fue comparar los resultados obtenidos mediante dos analizadores diferentes para la concentracion de IgG y de subclases de IgG. Materiales y metodos Se analizaron un total de 116 muestras de suero, independientemente del diagnostico clinico de los pacientes a los que pertenecian dichas muestras. Los analisis se realizaron sobre las plataformas BNII® System (Siemens Healthcare GmbH, Alemania) y Optilite® (The Binding Site Group Ltd., Birmingham). Resultados La correlacion entre la concentracion de IgG total (mg/dl) y el sumatorio de las concentraciones de subclases de IgG detectadas de manera individual fue mayor usando el analizador Optilite® (0,976 vs. 0,866). El porcentaje de concordancia vario del 43% hasta 71%, siendo el limite inferior para la concordancia de IgG3. Se detecto una ausencia de la proporcion fisiologica normal de subclases de IgG (IgG1 >IgG2 >IgG3 >IgG4) al utilizar BNII®. Dichos resultados fueron consecuencia de que la concentracion de IgG3 por BNII® fue significativamente inferior a la obtenida por Optilite® (p Conclusiones Las diferencias existentes entre los resultados obtenidos por ambos metodos analiticos utilizados sugieren que dichos ensayos no deben ser intercambiables, sino que cada laboratorio debe utilizar un unico analizador y estandarizar los rangos de referencia segun sus resultados.

Natural killer (NK) cells are lymphocytes of the innate immune response characterized by their role in the destruction of tumor cells. Activation of NK cells depend on a fine balance between activating and inhibitory signals mediated by different receptors. In recent years, a family of paired receptors that interact with ligands of the Nectin/Nectin-like (Necl) family has attracted great interest. Two of these ligands, Necl-5 (usually termed CD155 or PVR) and Nectin-2 (CD112), frequently expressed on different types of tumor cells, are recognized by a group of receptors expressed on T and NK cells that exert opposite functions after interacting with their ligands. These receptors include DNAM-1 (CD226), TIGIT, TACTILE (CD96) and the recently described PVRIG. Whereas activation through DNAM-1 after recognition of CD155 or CD112 enhances NK cell-mediated cytotoxicity against a wide range of tumor cells, TIGIT recognition of these ligands exerts an inhibitory effect on NK cells by diminishing IFN-γ production, as well as NK cell-mediated cytotoxicity. PVRIG has also been identified as an inhibitory receptor that recognizes CD112 but not CD155. However, little is known about the role of TACTILE as modulator of immune responses in humans. TACTILE control of tumor growth and metastases has been reported in murine models, and it has been suggested that it negatively regulates the anti-tumor functions mediated by DNAM-1. In NK cells from patients with solid cancer and leukemia, it has been observed a decreased expression of DNAM-1 that may shift the balance in favor to the inhibitory receptors TIGIT or PVRIG, further contributing to the diminished NK cell-mediated cytotoxic capacity observed in these patients. Analysis of DNAM-1, TIGIT, TACTILE and PVRIG on human NK cells from solid cancer or leukemia patients will clarify the role of these receptors in cancer surveillance. Overall, it can be speculated that in cancer patients the TIGIT/PVRIG pathways are upregulated and represent novel targets for checkpoint blockade immunotherapy.

The incidence of some types of tumours has increased progressively in recent years and is expected to continue growing in the coming years due in part to the aging of the population. The design of new therapies based on natural killer (NK) cells opens new possibilities especially for the treatment of elderly patients who are particularly susceptible to the toxicity of conventional chemotherapy treatments. In recent years, the potential use of NK cells in cancer immunotherapy has been of great interest thanks to advances in the study of NK cell biology. The identification of key points (checkpoints) in the activation of NK cells that can be regulated by monoclonal antibodies has allowed the design of new therapeutic strategies based on NK cells. However, there are still limitations for its use and the first clinical trials blocking KIR inhibitory receptors have shown little efficacy by inhibiting the maturation of NK cells. Blockade of other inhibitory receptors such as TIGIT, TIM3, LAG3 and PD1 may represent novel strategies to increase NK function in cancer patients. Altogether, the identification of NK cell and tumour cell markers of resistance or susceptibility to the action of NK cells will contribute to identifying those patients that will most likely benefit from NK cell-based immunotherapy.

Natural killer (NK) cells are a key component of innate immunity involved not only in the elimination of virus-infected or tumor cells but also in the regulation of the immune response by producing cytokines and chemokines that can activate other cellular components of innate and adaptive immunity. NK cell subsets are differentially affected by aging. Whereas CD56bright cells are decreased in healthy elderly individuals, the CD56dim subset is expanded. The expression of CD57, a marker of highly differentiated NK cells, is increased in the elderly; this supports the notion that a remodeling process of NK cell subsets occurs in aging with a gradual decrease in more immature CD56bright NK cells and an increase in highly differentiated CD56dim CD57+ NK cells. This NK cell redistribution can explain many of the phenotypic and functional changes in NK cells associated with healthy aging such as decreased proliferation and the maintenance of CD16-dependent cytotoxicity.

The expression on T lymphocytes of surface receptors that are characteristically expressed on NK cells has led to the definition of a T cell subset that has been termed Natural Killer T (NKT) cells. Thus NKT cells constitute a minor lymphocyte population that exhibits features of both T cells and NK cells. However, the term 'NKT cell' has been applied variably to cells that express a restricted T-cell receptor (TCR) that recognizes glycolipids (alpha-GalCer) presented by the MHC-like molecule CD1d and that express CD161, as well as populations of conventional CD8 T cells that show up-regulated expression of NK-cell markers. The CD1d restricted T cells have a semi-invariant TCR using the Valpha24Jalpha18 genes in humans (Valpha24Jalpha18 in mice) and are denominated invariant NKT (iNKT) cells. On the other hand mainstream T cells that express NK associated receptors (NKR) show a highly specialized effector memory phenotype and are frequently referred as NKT-like cells. These T lymphocyte subsets are differentially affected by ageing. Whereas human peripheral blood iNKT cells decrease with age, there is an increase in the percentage of peripheral blood NKT-like T lymphocytes.

Changes in the T cell pool caused by CMV infection have been proposed to contribute to immunosenescence, but it has been postulated that CMV can also have some beneficial effects in young individuals improving the immune response to other pathogens. T cells expressing CD56 (NKT-like cells) are cytotoxic effector cells with a significant role in the immune response against cancer. We have studied how age and latent CMV infection affect the frequency of NKT-like cells (CD8+ CD56+ T cells) and their response to Staphylococcal Enterotoxin B (SEB) in the context of CMV and ageing. NKT-like cell percentage increases with the combination of both CMV and age. The response to SEB and the polyfunctional index of NKT-like cells also increase with age in CMV-seropositive individuals. In young individuals, CMV infection induces a shift on the polyfunctional profile of CD8+ CD56- T cells not observed on the NKT-like cells response. NKT-like cells expressing CD57 are expanded in CMV-seropositive individuals and are more polyfunctional than their CD57- counterpart. In addition CD57- NKT-like cells are more polyfunctional than CD8+ CD56- CD57- T cells. The results support that the expansion of polyfunctional NKT-cells may have a beneficial effect on the immune response against pathogens.

People aged 60 and older represent over 11% of the world population and it is expected to rise 22% by 2050. Population aging is associated to an increased frequency of age-related diseases including higher susceptibility to infections, cancer, cardiovascular and neurodegenerative diseases. Immunosenescence refers to the decline of the immune system associated to aging. It affects both, innate and adaptive immunity limiting the response to pathogens and to vaccines. The analyses of the immune system in elderly individuals determined several immune signatures constituting an immune risk phenotype that predicts mortality. An inverse CD4/CD8 ratio, loss of naive T cells, increased numbers of terminally-differentiated T cells and oligoclonal expansions of virus-specific T cells constitute hallmarks of immunosenescence. Natural killer (NK) cells are also found severely altered in the elderly. The contribution of latent cytomegalovirus infection to immunosenescence of T and NK cells has been shown. Considering the worldwide ageing of the population in the next decades, the impact of infections will be a real health problem for older individuals requiring preventive strategies. Thus, further studies are required to analyse the bases of immunosenescence and to establish protocols to overcome the age-associated alterations of the immune response in order to define effective vaccines against those pathogens, such as influenza, contributing to increased morbidity and mortality in the elderly.

Aging is associated to dysfunctional changes in the immune system, a process termed immunosenescence. Elderly individuals usually present chronic low level inflammation, likely as the consequence of continued exposure to antigens combined with poor immune function, increases in production of pro-inflammatory cytokines by effector memory and senescent T cells and macrophages. This condition not only results from, but also drives immunosenescence. Aging affects all cell components of the immune system, including NK cells and its different subsets (CD56dimCD16+, CD56brightCD16+/− and CD56−CD16+). In particular, the percentage of total NK cells is increased in healthy aging and centenarians, whereas there is a decrease in the CD56bright NK cell subset and an expansion of CD56−CD16+ NK cells. However, the causes of these alterations on NK cells in old donors are not fully understood. In this work we analyse NK cell subsets in the elderly in relation with markers of inflammation and health status. The results show that there is a positive correlation between the number of total NK cells and the body mass index (BMI), while the number of CD56bright NK cells negatively correlates with the levels of C-reactive protein (CRP), supporting that chronic inflammation is involved in the decrease of this NK cell subset.

In humans, CD56, CD161, CD16, CD94 or CD57 represent prototypic markers of NK cells, although they are also found on a subset of CD8+ T cells. We propose here that the expression of NK receptors on CD8+ T cells can be considered a marker of cytotoxic effector T cells that are expanded in vivo after antigenic activation leading to extensive proliferation. The persistence of antigen will lead to loss of co-stimulatory molecules, telomere shortening and defective IL-2 production, changes that define the state replicative senescence in T lymphocytes. The majority of these "effector/senescent" T lymphocytes are CD8+, CD45RA+, CD11a(bright), CD28-, CD27-, CD62L- and CCR7-. They are cytotoxic T cells with strong expression of intracytoplasmic perforin and granzyme, but with low proliferative capacity and defective IL-2 production. Many of these characteristics are shared by the recently defined "effector/memory" T cells, being mainly distinguished by the absence of CD45RA expression on the memory cells. The expression of NK receptor in these effector cells will probably contribute to the regulation of their cytotoxic function. Expansion of cells with these characteristics can be found not only in the elderly but also in other clinical conditions involving chronic activation of the immune system such as viral infections, rheumatic and autoimmune diseases or tumors. Another subset of T cells that expresses the NK receptors is the alpha-galactosyl-ceramide specific T cell subset defined by the expression of canonical Valpha24JalphaQ TCR, recognition of CD1d and secretion of high amounts of IL-4 and IFN-gamma. However, the changes observed in the expression of NK-R on T cells associated to immunosenescence can not be attributed to expansion of this particular T cell subset, although alterations in the number and function of these cells have been demonstrated in some autoimmune diseases.

NK cells represent an important component of the innate immune response against infection and tumors. Age-associated changes in NK cell phenotype have been previously reported that can be responsible of functional NK cell deficiency. The aim of this work was to analyze the effect CMV seropositivity and aging on the distribution of NK cell subsets with a focus on the expression of cytotoxicity-related molecules and on the expression of CD94/NKG2 heterodimers and CD57 on these NK cell subsets. Our results show that CMV seropositivity in young individuals does not significantly affect peripheral blood NK cell percentage and NK cell subsets defined by the use of CD56 and CD16 markers. In contrast a significant increase in the percentage of NK cells is observed in elderly donors, all of them are CMV seropositive, when compared with young CMV seropositive subjects. A decrease in the percentage of CD56bright NK cells, either fully immature CD16 negative or CD16+ and an increase in the CD56-CD16+ subset are also found in the elderly. CMV seropositivity either in healthy young or elderly individuals is associated to the expression of CD94/NKG2C dimers and high expression of CD57on the CD56dimCD16+ NK cell subset. CD56-CD16+ NK cells, which are expanded in the elderly, show a decreased expression of granzymes A and B and an increased expression of CD94/NKG2C and CD57 in CMV seropositive young donors when compared with CMV seronegative young individuals. These results indicate that CMV and age have a different effect on NK cell phenotype and emphasize the relevance of including the determination of CMV serostatus in those studies addressed to analyze the immune response in the elderly.

Acute kidney failure in multiple myeloma (MM) occurs in 12%-20% of patients and is a poor prognostic factor for patient survival. Recent studies have shown that dialysis with a High-Cut-Off membrane (HCO) removes free light chains (FLC) effectively although with significant albumin loss. Other adsorption-based techniques, such as haemodiafiltration with ultrafiltrate regeneration by adsorption in resin (SUPRA-HFR), have not been studied. We present three cases of MM, all haemodialysis-dependent since diagnosis. Two cases were IgG kappa and one was IgA lambda. All patients were treated with chemotherapy and SUPRA-HFR. The aim of this study was to evaluate the effectiveness of SUPRA-HFR in the reduction of FLC and its effect on albumin. We collected blood samples pre- and post-dialysis, and ultrafiltrate (UF) samples pre- and post-resin 5 minutes into the session and 5 minutes from the end. The mean reduction rate of FLC in blood per session in the three patients was 53% and 63% (kappa) and 38% (lambda). In the UF, the mean FLC reduction rate was close to 99%, both at the start and at the end of dialysis, without the removal of albumin. With the results obtained we can conclude that this technique achieves an effective reduction of FLC, which is maintained throughout the session, without resin saturation and without albumin loss. Therefore, SUPRA-HFR is effective as an adjunctive therapy for MM.

NK cells are cytotoxic lymphocytes that are involved in the early defense against virus infected and tumor cells. NK cells exhibit the capacity to distinguish normal and damaged cells as well as self- and foreign cells. Besides their cytotoxic capacity NK cells also regulate the immune response by producing cytokines and chemokines that directly participate in the elimination of pathogens or activate other cellular components of immunity. NK cells express a broad range of activating receptors and their function is controlled by inhibitory receptors specific for the MHC class I molecules that are ubiquitously expressed on target cells.

Immunosenescence is a complex series of alterations that affect most aspects of immunity, including innate and adaptive immunity and is dependent not only on chronological ageing itself, but also on exogenous factors such as persistent antigenic stress leading to chronic activation of the immune system. The most significant changes occur in the T-cell compartment, with decreasing naive cells and increasing numbers of cells with a memory/activated phenotype. T-cells from elderly individuals also show altered responsiveness to antigen and display altered profiles of cytokine production when compared to T-cells from young individuals. The alterations in the T-cell compartment observed in the elderly have been implicated in the impaired immune response to viral infections and low response to vaccines. In particular, the most characteristic changes of the CD8 compartment associated with ageing are the accumulation of CD8+CD28null T-cells, antigen receptor repertoire shrinkage, increased expression of NK-associated receptors and the downregulation of CCR7 and CD45RA, suggesting an expansion of T-cells with an effector-memory 2 phenotype. These changes can be explained by the reduction of naive CD8+ T-cell-output, due to age-associated thymus involution and the oligoclonal expansion of CD8+ T-cells, likely as a consequence of persistent viral infections. The role of cytomegalovirus in the oligoclonal accumulation of CD8+CD28null T-cells has been recently stressed.

Human natural killer (NK) cells represent a heterogeneous lymphoid population involved in the recognition and lysis of tumor and virally infected cells. NK cells are defined by the expression of the IgG Fc receptor CD16 (FcγRIIIA) and/or CD56. NK cells do not rearrange immunoglobulin (Ig) or T-cell receptor (TCR) genes. Therefore, neither Ig nor the TCR-CD3 complex is expressed at the cell surface, except for the zeta (ζ) chain. Both markers, CD16 and CD56, have been used to analyze age-associated changes in the number of NK cells.

Natural killer T (NKT) cells represent a novel cell lineage characterized by the restricted expression of an invariant TCRalpha chain encoded by Valpha24/JalphaQ gene segments in humans and Valpha14/Jalpha281+ in mice. Different aspects of the immune response are severely affected by age. Thus, we have studied the effect of aging on NKT cells from healthy elderly individuals. Our results demonstrated a decreased percentage of CD3+Valpha24+ cells in peripheral blood from elderly donors, whereas mainstream T lymphocytes showed an age-associated decrease in the expression of CD28, the vast majority of CD3+Valpha24+ cells from old individuals were CD28+. A significant increase in the percentage of Valpha24+ cells with the CD4-CD8+ phenotype was also found in the elderly, indicating a redistribution of Valpha24+ subsets according to the CD4/CD8 phenotype. Given the important immunoregulatory role of these cells, the decrease of NKT cells will contribute to the deleterious immune response in the elderly.

The susceptibility to natural killer (NK) cell-mediated cytotoxicity of 20 cell lines obtained from human solid tumors and their class I histocompatibility antigen (HLA) levels were studied in an attempt to determine whether major histocompatibility complex (MHC) products expressed on cells derived from human solid tumors influence NK susceptibility. The effect of interferon-gamma (IFN-gamma) treatment on these elements was also analyzed. The MHC class I (HLA-ABC, HLA-A and HLA-B) antigen levels and degree of NK lysis were very heterogeneous and no correlation was found on comparison. After treatment with IFN-gamma a marked decrease in NK susceptibility was observed in all the cell lines, including the control line K-562. However, the level of HLA class I expression was not modified in any of the lines with the exception of the K-562, which increased. In some cell lines the expression of HLA class I-like antigens. CDla, b and c, was also measured before and after IFN treatment; however, no correlation was found between CD1 levels and NK susceptibility. Consequently, from our results it is possible to conclude that HLA class I antigens do not play a decisive role in NK susceptibility of cell lines derived from human solid tumors and to suggest that molecules which are not HLA class I antigens but IFN-gamma inducible may confer NK resistance to these lines.