Fas-Mediated Apoptosis Regulates the Composition of Peripheral αβ T Cell Repertoire by Constitutively Purging Out Double Negative T Cells

BACKGROUND: The Fas pathway is a major regulator of T cell homeostasis, however, the T cell population that is controlled by the Fas pathway in vivo is poorly defined. Although CD4 and CD8 single positive (SP) T cells are the two major T cell subsets in the periphery of wild type mice, the repertoire of mice bearing loss-of-function mutation in either Fas (lpr mice) or Fas ligand (gld mice) is predominated by CD4(-)CD8(-) double negative alphabeta T cells that also express B220 and generally referred to as B220+DN T cells. Despite extensive analysis, the basis of B220+DN T cell lymphoproliferation remains poorly understood. In this study we re-examined the issue of why T cell lymphoproliferation caused by gld mutation is predominated by B220+DN T cells. METHODOLOGY AND PRINCIPAL FINDINGS: We combined the following approaches to study this question: Gene transcript profiling, BrdU labeling, and apoptosis assays. Our results show that B220+DN T cells are proliferating and dying at exceptionally high rates than SP T cells in the steady state. The high proliferation rate is restricted to B220+DN T cells found in the gut epithelium whereas the high apoptosis rate occurred both in the gut epithelium and periphery. However, only in the periphery, apoptosis of B220+DN T cell is Fas-dependent. When the Fas pathway is genetically impaired, apoptosis of peripheral B220+DN T cells was reduced to a baseline level similar to that of SP T cells. Under these conditions of normalized apoptosis, B220+DN T cells progressively accumulate in the periphery, eventually resulting in B220+DN T cell lymphoproliferation. CONCLUSIONS/SIGNIFICANCE: The Fas pathway plays a critical role in regulating the tissue distribution of DN T cells through targeting and elimination of DN T cells from the periphery in the steady state. The results provide new insight into pathogenesis of DN T cell lymphoproliferation

The effector T cell response to influenza infection

Influenza virus infection induces a potent initial innate immune response, which serves to limit the extent of viral replication and virus spread. However, efficient (and eventual) viral clearance within the respiratory tract requires the subsequent activation, rapid proliferation, recruitment, and expression of effector activities by the adaptive immune system, consisting of antibody producing B cells and influenza-specific T lymphocytes with diverse functions. The ensuing effector activities of these T lymphocytes ultimately determine (along with antibodies) the capacity of the host to eliminate the viruses and the extent of tissue damage. In this review, we describe this effector T cell response to influenza virus infection. Based on information largely obtained in experimental settings (i.e., murine models), we will illustrate the factors regulating the induction of adaptive immune T cell responses to influenza, the effector activities displayed by these activated T cells, the mechanisms underlying the expression of these effector mechanisms, and the control of the activation/differentiation of these T cells, in situ, in the infected lungs

Determination Of Relaxation Time Spectra From Rheological Data Using An Edge Preserving Regularization Method

this article l is selected using the SC method due to Honerkamp and Weese (1990). In order to reconstruct even piecewise smooth spectra like the combination of the BSW and the CW spectrum we introduced the following representation of the a priori knowledge

Multiple mechanisms of tumorigenesis in E mu-myc transgenic mice.

Transgenic mice bearing a c-myc oncogene under control of the immunoglobulin heavy chain enhancer (E mu-myc mice) reproducibly develop and die from tumors of the B lymphocyte lineage (J.M. Adams, A.W. Harris, C.A. Pinkert, L.M. Corcoran, W.S. Alexander, S. Cory, R.D. Palmiter, and R.L. Brinster, Nature (Lond.), 318: 533-538, 1985; W.Y. Langdon, A. W. Harris, S. Cory, and J.M. Adams, Cell 47: 11-18, 1986; A.W. Harris, C.A. Pinkert, M. Crawford, W.Y. Langdon, R.L. Brinster, and J.M. Adams, J. Exp. Med., 167: 353-371, 1988; reviewed in S. Cory and J.M. Adams, Annu. Rev. Immunol., 6: 25-48, 1988). Analysis of lymphocytes obtained by serial sampling of peripheral blood from individual hemizygous (E mu-myc/0) and homozygous (E mu-myc/E mu-myc) transgenic mice indicates that proliferation in the original host and transplantability into histocompatible recipients are distinct properties that can be acquired independently and in either order. These two types of transgenic mice differ in that homozygous mice have about one-fourth the life span of hemizygous mice and develop polyclonal, non-transplantable tumors in comparison to the oligoclonal, highly transplantable malignancies seen in hemizygous animals. In conclusion, the overall concept of malignancy is best viewed as an aggregate of the separable parameters of cellular proliferation, clonality, tissue invasiveness, metastasis, and (experimental) transplantability. The E mu-myc transgenic mouse represents an attractive model in which to investigate the multistep nature and alternative pathways of tumorigenesis

Entwicklung eines flugtauglichen, laserspektroskopischen Spurengassensors und dessen Einsatz bei den TROPOZ-II- und SAFARI-Flugmesskampagnen Abschlussbericht

Im Rahmen dieses Vorhabens wurde ein Diodenlaser-Absorptionsspektrometer zur Spurengasmessung konstruiert und aufgebaut. Dieses Instrument, das an Bord eines Flugzeuges betrieben werden kann, ermoeglicht die simultane, quantitative Bestimmung von vier atmosphaerischen Spurengasen und wird nachfolgend als FLAIR-Spektrometer bezeichnet. Dieses FLAIR-Spektrometer wurde zum ersten mal im Rahmen der deutsch-franzoesischen Flugmesskampagne TROPOZ-II im Januar 1991 an Bord einer Caravelle 116 erfolgreich betrieben. Waehrend 22 Fluegen konnte die Verteilung von Kohlenmonoxid, Formaldehyd, Stickstoffdioxid und Wasserstoffperoxid auf einer globalen Skala (von 68 N bis 55 S, 0 bis 10 km Hoehe) gemessen werden. Im Rahmen des hier beschriebenen Vorhabens wurde das FLAIR-Spektrometer weiterhin bei einer zweiten Flugmesskampagne (SAFARI) eingesetzt. Ziel dieser Untersuchungen war die Beobachtung der Auswirkungen von Biomassenverbrennungen in einem regionalen Massstab. (orig./HM)Within the scope of this project, a tunable diode laser absorption spectrometer for trace gas measurement was designed and constructed. This instrument, which is capable of being operated onboard an aircraft, permits simultaneous quantitative determination of four atmospheric trace gases and is referred to as FLAIR (Four Laser Airborne Infrared) spectrometer. This FLAIR spectrometer was successfully operated within the framework of the Franco-German airborne measurement campaign TROPOZ II onboard a Caravelle 116 in January 1991. During 22 flights the distribution of carbon monoxide, formaldehyde, nitrogen dioxide and hydrogen peroxide was measured on a global scale (from 68 N to 55 S, 0 to 10 km altitude). Within the scope of the project described here the FLAIR spectrometer was also used during a second airborne measurement campaign (SAFARI). These investigations were designed to observe the effects of biomass combustion on a regional scale. (orig./HM)SIGLEAvailable from TIB Hannover: F94B0153+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman