Inferior vestibular neuritis: 3 cases with clinical features of acute vestibular neuritis, normal calorics but indications of saccular failure

BACKGROUND: Vestibular neuritis (VN) is commonly diagnosed by demonstration of unilateral vestibular failure, as unilateral loss of caloric response. As this test reflects the function of the superior part of the vestibular nerve only, cases of pure inferior nerve neuritis will be lost. CASE PRESENTATIONS: We describe three patients with symptoms suggestive of VN, but normal calorics. All 3 had unilateral loss of vestibular evoked myogenic potential. A slight, asymptomatic position dependent nystagmus, with the pathological ear down, was observed. CONCLUSION: We believe that these patients suffer from pure inferior nerve vestibular neuritis

Increased percentage of T cells with the expression of CD127 and CD132 in hypertrophic adenoid in children with otitis media with effusion

The hypertrophic adenoid may promote chronic suppurative otitis media in children as it fulfills its immune function. The number of lymphocytes in the adenoid and their cooperation in the immune response depend of on their proliferation and migration to the effector sites. Interleukin 7 (IL-7) is essential for the normal development and function lymphocytes. IL-7 plays pivotal role for activation and proliferation of T and B cells. The heterodimeric interleukin-7 receptor (IL-7R) is composed of the IL-7Rα (127) and the common cytokine receptor γc (CD132). The aim of this study was to evaluate the percentage of lymphocytes T (CD4+ and CD8+) with IL-7R (CD127 and CD132) expression in hypertrophic adenoid in children suffering with otitis media with effusion for a duration of 3 months. Adenoid excised due to hypertrophy with or without chronic otitis media with effusion was used as study material. CD4+ CD127+, CD4+132+, CD8+CD127+ and CD8+CD132+ cell subpopulations were identified using monoclonal antibodies and flow cytometry. The percentage of CD4+ and CD8+ T cells with CD127 receptor expression in hypertrophic adenoid of children with otitis media with effusion was statistically significantly higher than in hypertrophic adenoid group. The percentage of CD4+ T cells with CD132 expression in the study group was statistically significantly higher than in the reference group. The percentage of CD8+ T cells with CD132+ expression was not statistically different in both groups. The increased percentage of T lymphocytes with IL-7R expression (CD127 and CD132) in hypertrophic adenoid seems to influence the quantity of lymphocytes and upset the immunological function of tonsils which can influence the course of otitis media with effusion

IL-2 receptor γ chain cytokines differentially regulate human CD8+CD127+ and CD8+CD127− T cell division and susceptibility to apoptosis

Expression of IL-7 receptor α (CD127) is associated with naive and memory (i.e. non-effector) CD8+ T cell phenotypes. Effector CD8+ T cells are predominantly CD127− and most die by apoptosis. Therefore, CD127 appears to be a marker for CD8+ T cell differentiation, yet its role in CD8+ T cell survival and memory development is unclear. To address this, we investigated the cell death and cell division of isolated CD8+CD127+ and CD8+CD127− T cells in response to common IL-2 receptor γ chain (γC) cytokines other than IL-7. We show here that (i) memory cells (CD127+CD45RA−) divide frequently in response to either IL-2, -4 or -15; (ii) IL-2 and -15 enhance cell division in effector–memory-like cells (CD127−CD45RA+) while IL-4 enhances the cell division of effector cells (CD127−CD45RA−); (iii) CD8+CD127+ T cells are more sensitive to the anti-apoptotic effects of IL-2 or IL-15 than CD8+CD127− T cells and (iv) CD8+CD127+ T cell produce more Bcl-2 in response to IL-2 or IL-15 compared with CD8+CD127− T cells. Therefore, CD8+CD127+ and CD8+CD127− T cells differ in their responsiveness to cell division and anti-apoptotic signals from IL-2, -4 and -15. This suggests a role for γC cytokines in the pathogenesis of diseases in which CD127 expression is altered on CD8+ T cells such as in progressive viral infections and cancer

IL-7 Promotes CD95-Induced Apoptosis in B Cells via the IFN-γ/STAT1 Pathway

Interleukin-7 (IL-7) concentrations are increased in the blood of CD4+ T cell depleted individuals, including HIV-1 infected patients. High IL-7 levels might stimulate T cell activation and, as we have shown earlier, IL-7 can prime resting T cell to CD95 induced apoptosis as well. HIV-1 infection leads to B cell abnormalities including increased apoptosis via the CD95 (Fas) death receptor pathway and loss of memory B cells. Peripheral B cells are not sensitive for IL-7, due to the lack of IL-7Ra expression on their surface; however, here we demonstrate that high IL-7 concentration can prime resting B cells to CD95-mediated apoptosis via an indirect mechanism. T cells cultured with IL-7 induced high CD95 expression on resting B cells together with an increased sensitivity to CD95 mediated apoptosis. As the mediator molecule responsible for B cell priming to CD95 mediated apoptosis we identified the cytokine IFN-γ that T cells secreted in high amounts in response to IL-7. These results suggest that the lymphopenia induced cytokine IL-7 can contribute to the increased B cell apoptosis observed in HIV-1 infected individuals

The role of IL-7 in lymphopenia and bystander apoptosis during HIV-1 infection

The concentration of interleukin-7 (IL-7) in human serum is elevated in various clinical conditions associated with lymphopenia. IL-7 is an essential factor for T cell differentiation and survival, and high IL-7 concentration has been proposed to represent a homeostatic response to T cell depletion, which may accelerate thymic output and promote T cell regeneration. During HIV-1 infection, however, high levels of IL-7 are correlated with CD4+ T cell depletion and appear not to be beneficial to rescue the diminishing T cell pool. In order to further understand the impact of T cell numbers on serum IL-7 levels at different clinical stages of HIV-1 infection we investigated specimens from HIV-1 infected patients during primary and chronic infection and in long term non-progressors (LTNPs). In patients with primary HIV-1 infection, CD4+ and CD8+ T cell counts showed no correlation with the high IL-7 levels found in these patients; however the significant association seen between IL-7 and total CD3+ T cell counts may reflect an effect of lymphopenia on the increased IL-7 level, as previously reported in chronic HIV-1 infection. We also studied IL-7 levels in LTNPs, characterized by CD4+ T cell counts above 500 cells/μl and control of viral replication for 7 to 10 years without ART. Some of the LTNPs individuals progressed to a symptomatic phase of HIV-1 infection and, interestingly, we observed that these individuals showed a higher IL-7 level before progression as compared to the LTNPs that maintained high CD4+ T cell counts and virological control. We asked the question on whether positive effects of IL-7 on survival and homeostatic proliferation of T cells might be severely impaired in HIV-infected individuals due to IL-7Rα down-regulation. Thus the frequency of IL-7Rα- T cells in HIV-1 infected patients was studied in relation to CD4 Tcell counts, IL-7 concentration and expression in different T-cell populations. Down-regulation of IL-7Rα on T cells correlated with depletion of CD4 T cells (P < 0.001) and also with increased concentration of serum IL-7 (P < 0.05). Particularly, T cells with memory phenotype showed a decreased IL-7Rα expression in association with CD28 down-regulation. Thus, IL-7Rα downregulation and differentiation towards a CD28- memory phenotype in response to chronic activation may lead to an overall decrease of IL-7 mediated survival within the peripheral T-cell pool. The loss of CD4+ T cells during HIV-1 infection is not entirely the cause of direct infection of these cells, but is also due to bystander apoptosis where uninfected cells are predisposed to death inducing signals. As elevated IL-7 levels occur in HIV-infected individuals in addition to high Fas expression on T cells and increased sensitivity to Fas-induced apoptosis, we analyzed whether IL-7 has a regulatory role in Fas-mediated T cell apoptosis. We showed that IL-7 up-regulates in vitro Fas expression on naïve and memory T cells through a mechanism that involves translocation of Fas molecules from intracellular compartments to the cell membrane. The role of IL-7 in Fas upregulation in vivo was verified in IL-7 treated macaques. In addition IL-7 treatment primed T cells for Fas-induced apoptosis in vitro and serum IL-7 levels correlated with the sensitivity of T cells to Fas-induced apoptosis in HIV-infected individuals. Our data suggest that elevated IL-7 levels associated with HIV-1 infection, might participate in the increased sensitivity of T cells for activation-induced apoptosis. Alteration of receptor-mediated apoptosis is not limited to HIV-1 infection, but is also present in other infections including Leishmaniasis. Leishmaniasis infections often occur in areas of high HIV-1 prevalence. During Cutaneous Leishmaniasis (CL), caused by L. Major infection, there is a chronic inflammation process that leads to killing of the non-infected keratinocytes in the epidermis followed by disfiguring scar formations. Our studies showed that the expression of Fas, TRAIL-R2 and TRAIL is increased on keratinocytes upon exposure to supernatant from Leishmania infected PBMC cultures and in diseased skin from patients with CL. The expression of death receptors also renders the keratinocytes more sensitive to apoptosis and they can die through a bystander effect due to infiltrating immune cells expressing death ligands. Blocking Fas and TRAIL in vitro inhibits, to a great extent, apoptosis occurring in the experimental procedure