RESUMEN
Epidemiological data suggest that influenza vaccination protects against all-cause mortality in chronic obstructive pulmonary disease (COPD) patients. However, recent work has suggested there is a defect in the ability of some COPD patients to mount an adequate humoral response to influenza vaccination. The aim of our study was to investigate humoral and cell-mediated vaccine responses to the seasonal trivalent influenza vaccination (TIV) in COPD subjects and healthy controls. Forty-seven subjects were enrolled into the study; 23 COPD patients, 13 age-matched healthy controls (HC ≥ 50) and 11 young healthy control subjects (YC ≤ 40). Serum and peripheral blood mononuclear cells (PBMC) were isolated pre-TIV vaccination and at days 7 and 28 and 6 months post-vaccine for haemagglutinin inhibition (HAI) titre, antigen-specific T cell and antibody-secreting cell analysis. The kinetics of the vaccine response were similar between YC, HC and COPD patients and there was no significant difference in antibody titres between these groups at 28 days post-vaccine. As we observed no disease-dependent differences in either humoral or cellular responses, we investigated if there was any association of these measures with age. H1N1 (r = -0·4253, P = 0·0036) and influenza B (r = -0·344, P = 0·0192) antibody titre at 28 days negatively correlated with age, as did H1N1-specific CD4+ T helper cells (r = -0·4276, P = 0·0034). These results suggest that age is the primary determinant of response to trivalent vaccine and that COPD is not a driver of deficient responses per se. These data support the continued use of the yearly trivalent vaccine as an adjunct to COPD disease management.
Asunto(s)
Inmunidad Adaptativa/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/inmunología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/inmunología , Femenino , Pruebas de Inhibición de Hemaglutinación/métodos , Humanos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Leucocitos Mononucleares/inmunología , Masculino , Persona de Mediana Edad , Estaciones del Año , Vacunación/métodosRESUMEN
BACKGROUND: Cross-talk between skin keratinocytes (KCs) and Langerhans cells (LCs) plays a fundamental role in the body's first line of immunological defences. However, the mechanism behind the interaction between these two major epidermal cells is unknown. Interleukin (IL)-32 is produced in inflammatory skin disorders. We questioned the role of IL-32 in the epidermis. OBJECTIVES: We aimed to determine the role of IL-32 produced by KCs on surrounding LCs. METHODS: We used an ex vivo human explant model from healthy donors and investigated the role of IL-32 on LC activation using imaging, flow cytometry, reverse transcriptase quantitative polymerase chain reaction and small interfering (si)RNA treatment. RESULTS: Modified vaccinia virus ankara (MVA) infection induced KC death alongside the early production of the proinflammatory cytokine IL-32. We demonstrated that IL-32 produced by MVA-infected KCs induced modest but significant morphological changes in LCs and downregulation of adhesion molecules, such as epithelial cell adhesion molecule and very late antigen-4, and CXCL10 production. The treatment of KCs with IL-32-specific siRNA, and anti-IL-32 blocking antibody significantly inhibited LC activation, demonstrating the role of IL-32 in LC activation. We also found that some Toll-like receptor ligands induced a very high level of IL-32 production by KCs, which initiated LC activation. CONCLUSIONS: We propose, for the first time, that IL-32 is a molecular link between KCs and LCs in healthy skin, provoking LC migration from the epidermis to the dermis prior to their migration to the draining lymph nodes.
Asunto(s)
Comunicación Celular/inmunología , Interleucinas/metabolismo , Queratinocitos/inmunología , Células de Langerhans/inmunología , Adhesión Celular/inmunología , Células Cultivadas , Quimiocina CXCL10/inmunología , Quimiocina CXCL10/metabolismo , Quimiotaxis/inmunología , Dermatitis/inmunología , Dermatitis/virología , Voluntarios Sanos , Humanos , Interleucinas/genética , Interleucinas/inmunología , Queratinocitos/metabolismo , Ganglios Linfáticos/citología , Ganglios Linfáticos/inmunología , Cultivo Primario de Células , ARN Interferente Pequeño/metabolismo , Piel/citología , Piel/inmunología , Piel/metabolismo , Técnicas de Cultivo de Tejidos , Virus Vaccinia/inmunologíaRESUMEN
Qualitative and quantitative virological parameters were investigated in 68 long-term nonprogressor (LTNP) HIV-1-infected patients and 9 slow-progressor controls. LTNP status was defined as an asymptomatic HIV infection for at least 8 years, a stability of CD4+ cell counts > or =600 cells/mm3 and no antiretroviral therapy. LTNP subjects exhibited a lower median plasma RNA load than controls (6,000 vs. 40,000 RNA copies/ ml) despite a wide range of values in both groups. When compared to the control group, LTNP subjects also exhibited a lower virus isolation rate (65% vs. 100%) and cell-associated viremia (0.75 vs. 56.8 number of infectious unit/ million cells) when CD8-depleted CD4+ cells were tested. By contrast, no major differences in virus replication properties or cell tropism were observed. After 1 year of follow-up, no major overall changes in the virological parameters was observed in the 50 LTNP subjects evaluated at this time. However, nine patients had started antiretroviral therapy, and six others had increased viral loads. Despite the progression observed during the first year of follow-up, the hypothesis that there is a specific subgroup of LTNP patients who will not develop disease cannot be ruled out as yet.
Asunto(s)
Infecciones por VIH/virología , Sobrevivientes de VIH a Largo Plazo , VIH-1/fisiología , Carga Viral , Replicación Viral , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/virología , Estudios de Cohortes , ADN Viral/genética , Progresión de la Enfermedad , Estudios de Seguimiento , Infecciones por VIH/patología , VIH-1/genética , VIH-1/aislamiento & purificación , Células HeLa/citología , Células HeLa/virología , Humanos , Recuento de Linfocitos , Macrófagos/citología , Macrófagos/virología , ARN Viral/sangre , Factores de TiempoRESUMEN
The vigorous CTL response directed against HIV is considered to be important in reducing HIV viral load, although it is unable to stop ongoing viral replication, which generates new antigenic variants. We analyzed the impact of sequential changes in five epitopes of HIV-1 Nef on CTL recognition in four stable patients. A high rate of variation was found, and in all these patients we could detect CTL specific for 32 out of 36 autologous viral variants occurring in 5 HLA-A2- or HLA-B7-restricted Nef epitopes at two time points. Two distinct patterns for dynamics of CTL responses to viral variation were observed: 1) temporary amplification of viral variants followed by expansion of variant-specific CTL, ultimately leading to the disappearance of 12 out of the 14 initial epitope variants within two years. A second set of viral variants that had replaced the initial ones could also stimulate specific CTL precursors in the context of the same or an alternative HLA molecule; and 2) persistence of 2 viral variants in relatively conserved epitopes despite specific CTL recognition. Therefore, a remarkable flexibility of the immune system allows constant adaptation of CTL to multiple HIV variants and thus elimination of HIV variant-producing cells in slow progressors.