We demonstrate that TEM 00 mode optically pumped semiconductor lasers (OPSLs) may be scaled to tens of watts in the visible wavelength range using laser cavities an order of magnitude smaller than ...those of conventional solid-state lasers. In particular, we show that the output power may be scaled linearly by increasing the number of optically pumped semiconductor (OPS) devices and derive a unique solution for a dynamically stable resonator that is independent of the physical cavity length and internal design. This enables miniaturization of high-power OPS lasers to ~1 cm footprints without compromising many resonator performance metrics. The results are applied to demonstrate a 15-mm footprint cavity producing 7.3-W output at 486 nm, and a cavity with two OPS chips with 24-W output at 561 nm. In addition, we show that efficient TEM 00 mode performance may be realized using free-space-coupled, high-power laser diode bars. Single-frequency operation is also demonstrated, and an rms noise level less than 0.01% is achieved.
Role of ICOS versus CD28 in antiviral immunity Bertram, Edward M.; Tafuri, Anna; Shahinian, Arda ...
European journal of immunology,
December 2002, Letnik:
32, Številka:
12
Journal Article
Recenzirano
Odprti dostop
The costimulatory protein ICOS is inducibly expressed on activated T cells. Previous results have shown that ICOS–/– mice are defective in germinal center formation, antibody (Ab) production and ...class switch as well as Th1 and Th2 cytokine production in response to protein or parasite antigens. However, ICOS‐Ig failed to block antiviral Ab responses. To date the immune response to viruses has not been examined in ICOS–/– mice. In this report we compared antiviral Ab responses to LCMV, VSV and influenza virus in ICOS–/– versus wild‐type mice. Our results show that ICOS is important in the Ab response to all three viruses, with greater effects on primary as compared to secondary responses. Although ICOS–/– mice are impaired in some immune responses following influenza infection, the effects were less severe than for CD28–/– mice. There was no defect in initial influenza‐specific CD8 T cell expansion in ICOS–/– mice or in cytotoxic effector function. However, ICOS was important in maintaining CD4 cytokine production and CD8 T cell numbers late in the primary response. Upon secondary infection, ICOS–/– mice show wild‐type levels of influenza‐specific CD8 T cells, whereas CD28–/– mice show greatly impaired secondary CD8 T cell expansion. Overall, our results show that ICOS plays a clear role in the primary response to viruses at the level of Ab production, germinal center formation and Th cytokine production, but has diminished effects following secondary viral challenge.
Mutations in viral genomes that affect T-cell-receptor recognition by CD8+ cytotoxic T lymphocytes have been shown to allow viral evasion from immune surveillance during persistent viral infections. ...Although CD4+ T-helper cells are crucially involved in the maintenance of effective cytotoxic T-lymphocyte and neutralizing-antibody responses, their role in viral clearance and therefore in imposing similar selective pressures on the virus is unclear. We show here that transgenic virus-specific CD4+ Tcells, transferred into mice persistently infected with lymphocytic choriomeningitis virus, select for T-helper epitope mutant viruses that are not recognized. Together with the observed antigenic variation of the same T-helper epitope during polyclonal CD4+ T-cell responses in infected pore-forming protein-deficient C57BL/6 mice, this finding indicates that viral escape from CD4+ T lymphocytes is a possible mechanism of virus persistence.
The expression of the prion protein (PrP) in the follicular dendritic cell network of germinal centers in the spleen is critical for the splenic propagation of the causative agent of prion diseases. ...However, a physiological role of the prion protein in the periphery remains elusive. To investigate the role and function of PrP expression in the lymphoid system we treated naive mice i.v. with preformed immune complexes or vesicular stomatitis virus. Immunohistochemistry and Western blot analysis of the spleen revealed that 8 days after immunization, immune complexes and vesicular stomatitis virus had both induced a strong increase of PrP expression in the follicular dendritic cell network. Remarkably, this up-regulation did not occur in mice that lack an early factor of the complement cascade, C1q, a component which has been shown previously to facilitate early prion pathogenesis. In addition to the variable PrP level in the germinal centers, we detected steady and abundant PrP expression in the splenic capsule and trabeculae, which are structural elements that have not been associated before with PrP localization. The abundant trabeculo-capsular PrP expression was also evident in spleens of Rag-1-deficient mice, which have been shown before to be incapable of prion expansion. We conclude that trabeculocapsular PrP is not sufficient for splenic prion propagation. Furthermore, our observations may provide important clues for a physiological function of the prion protein and allow a new view on the role of complement and PrP in peripheral prion pathogenesis.
Rapid disappearance of antiviral CTL after transfusion into persistently infected individuals is a serious limitation of adoptive immunotherapy protocols. In the mouse model of persistent infection ...with lymphocytic choriomeningitis virus (LCMV) naive or immune virus‐specific donor CD8+ T cells are exhausted after transfusion into carrier recipients with similar kinetics. Here weshow that cotransfusion of immune CD4+ T cells prevents exhaustion of immune CD8+ T cells. Interestingly, cotransfer of primed B cells also prevented CD8+ T cell exhaustion in carriers even in the absence of T helper cells. This effect required the presence of immune B cells as repetitive treatment with hyperimmune serum led to the generation of antibody escape mutants. A combination of primed CD4+ T cells and primed B cells enhanced antiviral effects and prevented exhaustion also of naive CD8+ T cells. One key factor for prevention of CD8+ T cell exhaustion was the antiviral effect of the cotransfused cells thus reducing the time that CD8+ T cells are confronted with a high systemic viral load. These findings have implications for improving adoptive immunotherapy for persistent human viral infections.
Experimental autoimmune myocarditis (EAM) represents a Th17 T cell-mediated mouse model of postinflammatory heart disease. In BALB/c wild-type mice, EAM is a self-limiting disease, peaking 21 days ...after alpha -myosin H chain peptide (MyHC- alpha )/CFA immunization and largely resolving thereafter. In IFN- gamma R super(-/-) mice, however, EAM is exacerbated and shows a chronic progressive disease course. We found that this progressive disease course paralleled persistently elevated IL-17 release from T cells infiltrating the hearts of IFN- gamma R super(-/-) mice 30 days after immunization. In fact, IL-17 promoted the recruitment of CD11b super(+) monocytes, the major heart-infiltrating cells in EAM. In turn, CD11b super(+) monocytes suppressed MyHC- alpha -specific Th17 T cell responses IFN- gamma -dependently in vitro. In vivo, injection of IFN- gamma R super(+/+)CD11b super(+), but not IFN- gamma R super(-/-)CD11b super(+), monocytes, suppressed MyHC- alpha -specific T cells, and abrogated the progressive disease course in IFN- gamma R super(-/-) mice. Finally, coinjection of MyHC- alpha -specific, but not OVA-transgenic, IFN- gamma -releasing CD4 super(+) Th1 T cell lines, together with MyHC- alpha -specific Th17 T cells protected RAG2 super(-/-) mice from EAM. In conclusion, CD11b super(+) monocytes play a dual role in EAM: as a major cellular substrate of IL-17-induced inflammation and as mediators of an IFN- gamma -dependent negative feedback loop confining disease progression.
Lymphocytic choriomeningitis virus (LCMV) represents a useful experimental model of murine infection with a non-cytopathic virus, bearing resemblance to HIV and hepatitis C virus (HCV) infections in ...humans. Recent data from the LCMV model indicate that the humoral immune response that is induced by non-cytopathic viruses is far more complex than previously appreciated. LCMV-induced IgG production is largely polyclonal, with more than 90% of the antibody repertoire constituting non-relevant specificities. A delayed virus-neutralizing antibody response is induced, including specificities directed not only against the parental LCMV-strain present in the host but also cross-specifically against LCMV-variants isolated from other hosts. These findings provide novel insights to aid our understanding of clinically relevant observations that are recorded following human infection with HIV, HCV and dengue viruses.
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