T cells in the liver: there is life beyond the graveyard

Influenza A virus infection of C57BL/6 mice is a well-characterized model for studying CD8+ T cell-mediated immunity. Analysis of primary and secondary responses showed that the liver is highly enriched for CD8+ T cells specific for the immunodominant H2D(b)NP(366-374) (D(b)NP(366)) epitope. Functional analysis established that these liver-derived virus-specific CD8+ T cells are fully competent cytotoxic effectors and IFN-gamma secretors. In addition, flow cytometric analysis of early apoptotic cells showed that these influenza-specific CD8+ T cells from liver are as viable as those in the spleen, bronchoalveolar lavage, mediastinal lymph nodes, or lung. Moreover, cytokine profiles of the influenza-specific CD8+ T cells recovered from different sites were consistent with the bronchoalveolar lavage, rather than liver population, being the most susceptible to activation-induced cell death. Importantly, adoptively transferred influenza virus-specific CD8+ T cells from the liver survived and were readily recalled after virus challenge. Together, these results show clearly that the liver is not a "graveyard" for influenza virus-specific CD8+ T cells.     

The liver: a special case in transplantation tolerance

Liver transplants are not often rejected in patients weaned from immunosuppression and are spontaneously accepted in some animal models. We review past and recent findings of liver transplantation and propose a unified model in which several mechanisms act in concert to induce and maintain tolerance in both na?ve and effector T cell compartments. First, passenger leukocytes migrate to lymphoid tissues and induce apoptosis of alloreactive na?ve T cells. Second, antigen-specific activation and subsequent deletion of na?ve and effector cells within the liver itself purge the repertoire of alloreactive T cells. Other mechanisms such as microchimerism and migration of donor dendritic cells to the thymus may play a predominant role in maintaining tolerance, and soluble major histocompatibility complex molecules, donor peptides, and regulatory T cells may participate in the induction and maintenance phases. Thus, the major challenge in liver transplantation will be to favor these tolerogenic processes while developing strategies that specifically inhibit alloreactive memory T cells.     

Living with autoinflammatory diseases: identifying unmet needs of children,adolescents and adults

Background

Autoinflammatory diseases (AIDs) illnesses of the innate immunity resulting in clinical signs and symptoms of systemic inflammation and loss of organ functions. While pathophysiological mechanisms are heavily studied and increasingly well understood, psychosocial needs are much less explored. The disease impact on the everyday life of patients including school and work is poorly studied. The purpose of the study was to identify the spectrum of unmet needs of children, adolescents and adults living with autoinflammatory disease and their families, to define key unmet needs and strategies and to develop and evaluate a pilot intervention addressing the unmet need “school”.

Methods

A single-center, mixed-method study of AID patients and their families was conducted. Consecutive patients ages ≥4?years and their families were included. Expert consulting, focus groups and questionnaires explored the patient perspective of “unmet needs in AID”. Quantitative and qualitative content analyses were performed and informed the development of a framework of unmet needs. A targeted pilot multimodular intervention for the unmet need “school” was developed and tested. Health-related Quality of Life (HRQoL) was evaluated using DISABKIDS-questionnaires and psychosocial impact evaluations.

Results

The study included 83 patients and their families. These were 14 children, 9 adolescents and 25 adults with AID and 35 family members; patients’ median age was 19?years (5–78). Expert consultations: 110 AID patients with 320 visits/year; 99 (90%) were children and adolescents. 78 patients and family members (94%) participated in 10 groups. Qualitative content analysis delineated 9 domains of unmet needs, the most relevant being school, health care system and public institutions. The pilot intervention“school” included 18 participants; median age was 9?years (7–16). HRQoL improved with the intervention including “understanding” by 53%, however improvement was not sustained over time.

Conclusion

Unmet needs of AID patients and families affect all areas of life. Accessible networks increasing knowledge and empowering patients, strategies supporting academic and workplace environments to ensure successful participation and integrated concepts addressing psychosocial needs are urgently needed.

     

Progressive familial hearing loss in Muckle-Wells syndrome

Conclusion. The tumor size of acoustic neuroma correlates with cochleovestibular deficits. Those tumors with global frequency hearing loss, bilateral gaze nystagmus, or absent caloric and VEMP responses may indicate a tumor size >2.5 cm. Objective. This study aimed to investigate the correlation between cochleovestibular deficits and the size of acoustic neuroma. Patients and methods. A total of 44 patients with acoustic neuroma were enrolled in this study. Pure tone audiometry, electronystagmography, caloric test, vestibular evoked myogenic potential (VEMP) test, and MRI were conducted. Results. There is a trend of correlation between tumor size and audiographic configuration, with small-sized tumor in normal and rising types, medium-sized tumor in mid- and high-frequency hearing loss, and large-sized tumor in flat and deafness types. Five patients with bilateral gaze nystagmus had significantly larger tumor size than those without nystagmus. When 1 and 0 are used to represent abnormal and normal responses, respectively, the relationship between tumor size and vestibular function can be expressed as: tumor size (cm)=1.43 (caloric response)+1.35 (VEMP response), indicating that the estimated tumor size for those with abnormal caloric or VEMP responses increased by 1.43 or 1.35 cm, respectively.