Three-dimensional (3-D) imaging of fluorescence resonance energy transfer (FRET) in human cells under two-photon excitation was demonstrated in this study. A sample was prepared by expressing a donor and an acceptor in living cells and using an antibody to secure the proximity of contact between the donor and the acceptor. The quenching of fluorescence emission of a donor in the double-labelled cells indicates the presence of FRET that occurred in these living cells. Because of the quadratic relation of the excitation power, 3-D localisation of FRET becomes possible.

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PubMedDate not supplied

Inhibition of pathogenic effect of effector T cells by specific suppressor T cells during influenza virus infection in mice.

Mice infected with an aerosol of influenza type A virus, or immunized with purified UV-inactivated whole virus or with viral subunits, develop a transient delayed-type hypersensitivity (DTH) which peaks 5-7 days after immunization. The intensity of DTH is greatly enhanced and sustained when mice are pretreated with cyclophosphamide. The reaction is maximal 24 h after elicitation, has classical tuberculin-type histology and is transferable by immune H-21 region restricted Lyt-1+2- T cells (Td) but not by immune serum. These Td cells not only fail to protect mice against influenza virus infection, but increase the mortality rate due to influenzal pneumonia following challenge with homologous lethal virus. On the other hand, antigen-specific suppressor T (Ts) cells which inhibit DTH are readily generated during influenza virus infection, and are detectable for at least 40 days thereafter. The ease with which they are induced and maintained during the infection may be of evolutionary advantage. In support of this, we now report that these Ts cells can reverse the pathogenic effect of Td cells thereby demonstrating a beneficial influence of Ts cells in a viral disease.

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PubMedDate not supplied

Properties of monoclonal antibodies to human tumor necrosis factor alpha (TNF alpha).

Four murine monoclonal antibodies were produced against human recombinant tumor necrosis factor alpha (TNF alpha). They were characterized with respect to specificity, affinity, neutralization of in vitro L929 cell killing by TNF alpha and neutralization of the in vivo biological activities of toxicity and tumor necrosis. The monoclonal antibodies were further investigated for reactivity with TNF alpha in Western blotting. All four monoclonal antibodies reacted with human TNF alpha. One of then also reacted with mouse TNF alpha and human TNF beta (lymphotoxin), this antibody did not neutralize in vitro cytotoxicity or in vitro biological activities of TNF alpha. The other antibodies were neutralizing and it appeared that, in some cases, the systemic toxic effect of TNF alpha could be reversed by anti-TNF alpha monoclonal antibody therapy while retaining significant anti-tumour effects.

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PubMedDate not supplied

A mouse model of influenza protection.

A mouse model has been developed in order to examine the parts played by humoral and cellular mechanisms in influenza immunity. Protection is assessed in terms of the amount of virus detectable in the lungs within 48 h of challenge. This system has two major advantages over the more common mouse lethality models. It is no longer necessary to use a mouse-lethal strain of virus; and protection is measured within days rather than weeks of challenge. Thus it is possible to determine the ability of the immune system to limit infection at an early stage, as distinct from curing a pre-existing infection and so preventing death. Transfer of spleen cells from an immune donor to a normal recipient will significantly reduce the amount of virus found in the lungs 24 h after challenge. The transferred cells are, however, capable of producing significant serum levels of anti-influenza antibody. Administration of serum from immune mice to normal recipients also results in a significant degree of protection within 24 h of challenge. These results give additional evidence that in the mouse significant protection is provided by serum antibody very soon after infection, but do not exclude the possibility that a part may be played by other mechanisms.

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