Naive and central memory CD8 T cells use CCR7 to recirculate through T cell zones of secondary lymphoid organs where they can encounter antigen. Here we describe a subset of human CD8 T cells expressing CXCR5 which enables homing in response to CXCL13 produced within B cell follicles. CXCR5 + CD8 T cells were found in tonsil B cell follicles, and isolated cells migrated towards CXCL13 in vitro. They expressed CD27, CD28, CD45RO, CD69, and were CD7 low , and produced IFN-c and granzyme A but lacked perforin, a functional profile suggesting that these cells are early effector memory cells in the context of contemporary T cell differentiation models. Receptors important in the interaction with B cells, including CD70, OX40 and ICOS, were induced upon activation, and CXCR5 + CD8 T cells could to some extent support survival and IgG production in tonsil B cells. Furthermore, CXCR5 + CD8 T cells expressed CCR5 but no CCR7, suggesting a migration pattern distinct from that of follicular CD4 T cells. The finding that a subset of early effector memory CD8 T cells use CXCR5 to locate to B cell follicles indicates that MHC class I-restricted CD8 T cells are part of the follicular T cell population. IntroductionCD8 T cells are lymphocytes of the adaptive immune system which recognize viral and bacterial peptides presented by MHC class I molecules and are indispensable in the control of many intracellular infections [1]. When appropriately stimulated by antigen presented by dendritic cells (DC) in secondary lymphoid tissues, they proliferate vigorously, become effector cells, and upon resolution of infection a small population of antigen-specific CD8 T cells are maintained as long-lived memory cells [2][3][4]. A primary effector mechanism of CD8 T cells is the killing of infected cells via the targeted release of the lytic effector molecules perforin and granzymes, and via expression of death receptors. However, there is significant functional heterogeneity in CD8 T cells and they are also efficient in producing anti-viral and pro-inflammatory cytokines [5][6][7][8]. The effector mechanisms used may depend on the pathogen and on the type of cell or tissue that is infected [8].CD8 T cell responses involve the differentiation of naive T cells into distinct types of effector and memory cells [2, 3,9]. One approach to analyse a T cell response is to examine the expression of receptors that mediate homing of T cells, such as CD62L, which binds to glycosylation-dependent cell adhesion molecule 1 on [4,20,21]. CXCR5 is a chemokine receptor which is expressed on all B cells and on specialized subsets of DC and T cells [22]. It has only one known ligand, the chemokine CXCL13, mainly produced by stromal cells and follicular DC within B cell follicles [23][24][25]. CXCR5 + CD4 T cells, known as follicular homing T helper cells, are found in B cell follicles and contribute to the generation of effective humoral immune responses by supporting antibody production and isotype class switching [26,27]. However, some of the processes and mec...
The circulatory function in normal young adults has been studied by heart catheterization both at rest and during exercise. The reports include both ordinarily trained individuals and athletes (for references see 5, 6, 17, 37). Elderly subects, however, have not previously been studied by this technique, but by dye dilution the cardiac output and stroke volume at rest in elderly subjects were found to be lower than in young adults (7).The present study formed part of a more detailed investigation of the circulatory function in old men (30-35). Besides, it was found necessary to collect catheterization data for healthy elderly subjects as the central circulation is nowadays studied for diagnostic reasons in an increasing number of elderly patients. Because most routine catheterizations are performed in supine and most studies on exercise physiology in sitting position, the subjects were studied in both positions. A preliminary report has been issued on the findings concerning the first subjects studied (14).
Taken together, these findings demonstrate that there was a broad and early immune activation in GALT and pLT during acute HIV-1 infection. The relative lack of perforin expression in both GALT and pLT, however, questions the functional efficacy of the observed immune activation in generating cytotoxic T cells that were able to eliminate HIV-infected cells.
Immune responses were assessed at the single-cell level in lymph nodes from children with tuberculous lymphadenitis. Tuberculosis infection was associated with tissue remodeling of lymph nodes as well as altered cellular composition. Granulomas were significantly enriched with CD68+ macrophages expressing the M. tuberculosis complex-specific protein antigen MPT64 and inducible nitric oxide synthase. There was a significant increase in CD8+ cytolytic T cells surrounding the granuloma; however, CD8+ T cells expressed low levels of the cytolytic and antimicrobial effector molecules perforin and granulysin in the granulomatous lesions. Quantitative real-time mRNA analysis revealed that interferon-gamma, tumor necrosis factor-alpha, and interleukin-17 were not up-regulated in infected lymph nodes, but there was a significant induction of both transforming growth factor-beta and interleukin-13. In addition, granulomas contained an increased number of CD4+FoxP3+ T cells co-expressing the immunoregulatory cytotoxic T-lymphocyte antigen-4 and glucocorticoid-induced tumor necrosis factor receptor molecules. Low numbers of CD8+ T cells in the lesions correlated with high levels of transforming growth factor-beta and FoxP3+ regulatory T cells, suggesting active immunosuppression at the local infection site. Compartmentalization and skewing of the immune response toward a regulatory phenotype may result in an uncoordinated effector T-cell response that reduces granule-mediated killing of M. tuberculosis-infected cells and subsequent disease control.
Purpose of ReviewTo survey current strategies for treatment and prevention of recurrent acute otitis media (rAOM).Recent FindingsTreatment with systemic antibiotics is required in recurrent episodes of acute otitis media. A cautious attitude is recommended due to antibiotic resistance. Antibiotics also provide effective prophylaxis for rAOM. Topical treatment with ear drops is recommended in rAOM with otorrhea from tympanostomy tubes. Pneumococcal conjugated vaccines seem to have a moderate reductive effect on overall otitis media. The effect on rAOM is still unclear. Different administrations of immunoglobulins have not been effective against rAOM. Breastfeeding had a protective effect against rAOM. A recommendation against cigarette smoke exposure as a measure to prevent otitis seems warranted. An effect for adenoidectomy in children <2 years old with rAOM has been suggested. There is a strong genetic connection with rAOM. Probiotics and nasal spray with Streptococci might offer future opportunities as prophylaxis. Too little is known about complimentary treatments to give any recommendations.SummarySystemic antibiotics are still needed as treatment against episodes of AOM in rAOM children. There are several preventive measures that can be taken to reduce the burden of AOM but they all have a small-moderate effect. Systemic antibiotics provide effective prophylaxis in rAOM, but must be used with extreme caution due to the emerging antibiotic resistance.
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