Programmed cell death of T lymphocytes during acute viral infection: a mechanism for virus-induced immune deficiency.

Acute viral infections induce immune deficiencies, as shown by unresponsiveness to mitogens and unrelated antigens. T lymphocytes isolated from mice acutely infected with lymphocytic choriomeningitis virus (LCMV) were found in this study to undergo activation-induced apoptosis upon signalling through the T-cell receptor (TcR)-CD3 complex. Kinetic studies demonstrated that this sensitivity to apoptosis directly correlated with the induction of immune deficiency, as measured by impaired proliferation in response to anti-CD3 antibody or to concanavalin A.

The monoclonal antibody CZ-1 identifies a mouse CD45-associated epitope expressed on interleukin-2-responsive cells.

We have previously described a monoclonal antibody (mAb), CZ-1, which reacts with an epitope expressed on most peripheral basophils, natural killer cells, B cells, and CD8+ T cells, but not with most thymocytes or peripheral CD4+ T cells. Here we show that mAb CZ-1 defines a sialic acid-dependent epitope associated with a subpopulation of CD45 molecules. This conclusion is based on the ability to block binding of mAb CZ-1 by sialic acid, neuramin-lactose, neuraminidase, and mAb to CD45RB, and by expression of the epitope on transfected psi 2 cells expressing exon B of CD45.

Reestablishment of lymphatic drainage after canine lung transplantation.

The technique of pulmonary lymphoscintigraphy was used to evaluate pulmonary lymphatic flow and to assess reestablishment of lymphatic drainage after lung transplantation. A first group of six control dogs underwent percutaneous transthoracic injection of a radiocolloid into the periphery of the left upper and lower lobes. Radiocolloids are large molecules tagged with radioisotopes that are absorbed only through lymph and are concentrated in tributary lymph nodes.

B cells induce apoptosis via a novel mechanism in fibroblasts infected with mouse hepatitis virus.

B cells from nonimmune mice mediate the cytolysis of fibroblasts infected with the coronavirus, mouse hepatitis virus (MHV), strain A59. In this investigation, we report that splenic B cells and a B cell hybridoma induced the fragmentation of MHV-infected target cell DNA into a nucleosomal ladder pattern, characteristic of apoptosis. To determine the mechanism by which B cells mediated this killing event, we used criteria previously established for the killing of target cells by cytotoxic T lymphocytes (CTLs) and compared this B-cell-mediated killing to lymphocytic choriomeningitis virus (LCMV)-specific CTL killing of LCMV-infected target cells.

Repair of nonunion of tibial osteotomy.

Nonunion after high tibial osteotomy is an uncommon complication. Ten cases have been treated with a single plate; failure occurred twice in five. Double plates, bolted together, healed in all five attempts.

High frequency of cross-reactive cytotoxic T lymphocytes elicited during the virus-induced polyclonal cytotoxic T lymphocyte response.

Polyclonal stimulation of CD8+ cytotoxic T lymphocytes (CTL) occurs during infection with many viruses including those not known to transform CTL or encode superantigens. This polyclonal CTL response includes the generation of high levels of allospecific CTL directed against many class I haplotypes. In this report we investigated whether the allospecific CTL generated during an acute lymphocytic choriomeningitis virus (LCMV) infection of C57BL/6 mice were stimulated specifically by antigen recognition or nonspecifically by polyclonal mechanisms possibly involving lymphokines or superantigens.

A method for the preparation of DNA from calf thymus nuclei in maximum purity and yield, analysis of this DNA compared with that obtained by other methods.

In the preparation of calf thymus DNA, a method (1) was developed to yield DNA in maximum yield and purity, with a minimum of shear degradation, which differed in three respects from those used in standard preparations: 1) use of calf thymus nuclei rather than whole tissue as a source of the DNA; 2) use of initial Pronase, then on the next cycle RNAase + Pronase digestions; 3) use of optimal concentrations of reagents to precipitate denatured proteins in the purification cycles. The optimal reagent concentrations were determined in tests by changing each variable one at a time to be 3M NaCl, 3% sarcosyl. The purification cycles consisted of adjustment of DNA solution in buffer to 3M NaCl-3% sarcosyl, centrifugation, alcohol precipitation, and redissolving DNA fibers in buffer.

Comparison of Doppler echocardiography and cardiac catheterization in patients requiring valve surgery: search for a 'gold standard'.

Objective: To compare the sensitivities of Doppler echocardiography and cardiac catheterization in the diagnosis of severe valvular heart disease in patients requiring valve surgery.

Design: Retrospective analysis of Doppler echocardiograms and cardiac catheterizations.

Setting: Tertiary referral cardiovascular centre in a university setting.

CD11b (Mac-1): a marker for CD8+ cytotoxic T cell activation and memory in virus infection.

We have found that CD11b, a cell surface integrin of macrophages, granulocytes, and NK cells, is expressed by a subset of CD8+ T cells that include both the active virus-specific CTL and the virus-specific memory CTL populations. CD8+CD11b+ cells comprise less than 3% of naive mouse splenocytes, but after lymphocytic choriomeningitis virus (LCMV) infection increase by 9- to 12-fold by the peak (day 8) of the virus-specific CTL response. Depletion of day-8 splenocytes with anti-Mac-1 and C' or enrichment by sorting for CD11b+ or CD8+CD11b+ spleen cells demonstrated that LCMV-specific CTL are CD11b+.

Epizootic of Yersinia pseudotuberculosis in a wildlife park.

An epizootic attributable to Yersinia pseudotuberculosis infection was confirmed in captive ruminants in a wildlife park by microbiologic and histologic findings. An epornitic of Y pseudotuberculosis infection was identified at the same period in a vicinity near the ruminant deaths. Yersinia pseudotuberculosis can infect human beings and cause acute enteritis and mesenteric lymphadenitis.

Window of vulnerability of vaccinia virus-infected cells to natural killer (NK) cell-mediated cytolysis correlates with enhanced NK cell triggering and is concomitant with a decrease in H-2 class I antigen expression.

A time course study was performed in order to determine if vaccinia virus (VV)-infected targets were more susceptible to murine natural killer (NK) cell-mediated lysis during a discrete period of time postinfection. Activated NK cells were used in short-term (e.g.

Generation of "natural killer cell-escape" variants of Pichinde virus during acute and persistent infections.

Pichinde virus (PV) strain AN 3739 was determined to be sensitive to natural killer (NK) cells in vivo by enhanced replication in NK-cell-depleted mice. An NK-sensitive subclone (PV-NKs1) was serially passed in mice whose NK cells had previously been activated by an interferon inducer, and two plaque isolates were shown to be resistant to NK cells but not to interferon. Inoculation of severe-combined-immunodeficient mice with PV-NKs1 led to a persistent infection resulting in an NK-resistant viral population.

A lymphocyte differentiation and activation antigen, CZ-1, that distinguishes between CD8+ and unstimulated CD4+ T lymphocytes.

We report the generation and cellular reactivity of a novel rat IgM monoclonal antibody (mAb), CZ-1, made against mouse natural killer (NK) cells activated in vivo. mAb CZ-1 recognizes a molecule whose properties are consistent with that of a trypsin-sensitive, non-phosphatidyl inositol-linked sialoglycoprotein. The expression of the antigen recognized by mAb CZ-1 is restricted mostly to cells of the lymphoid lineage.

Inhibition of cytotoxic T lymphocyte-induced target cell DNA fragmentation, but not lysis, by inhibitors of DNA topoisomerases I and II.

Cytotoxic T lymphocytes (CTL) kill their target cells via a contact-dependent mechanism that results in the perturbation of the target cell's plasma membrane and the fragmentation of the target cell's DNA into nucleosomal particles. The membrane disruption is presumed to be due to the action of perforin, while the DNA fragmentation is thought to be by the activation of an endogenous nuclease(s). DNA topoisomerases I and II are nuclear enzymes with inherent endonuclease activities.