The effect of virus on the cytotoxic effector function of normal human lymphocytes

• The cytotoxic effect of human peripheral blood lymphocytes (PBL) from healthy donors against mumps virus infected cells was studied by 5lCR-release assay. With several different cell fractionation techniques the effector cells were demonstrated to be undistinguishable from the lymphocytes responsible for antibody dependent cellular cytotoxicity (ADCC, K-cells) and from those responsible for natural cytotoxicity (NK cells). In these three cytolytic systems the effector cells have Fc receptors for IgG (FcR). While ADCC is dependent on antibody by definition, NK activity involves both antibody dependent and antibody independent mechanisms. To learn whether the killing of virus infected cells required antibody. Fab fragments of rabbit antibodies to human immunoglobulin were added to the PBL-target cell mixtures. This reagent failed to inhibit the virus dependent target cell lysis, implying that the; reaction was immunoglobulin independent. Binding of PBL to target cells by the virus did not seem to be sufficient to cause target cell lysis since a PBL subset which also adhered firmly to virus infected cells did not lyse those. However, a virus induced cross linking of effector cells and target cells may facilitate the expression of cytotoxicity. Exposure of PBL to small amounts of mumps virus results in an enhanced cytolytic activity against uninfected target cells. Also in this instance were the effector cells closely related to the K- and NK-cells. Virus dependent cytotoxicity was not due to an ADCC type of mechanism as it remained essentially unchanged when the FcR activity of the lymphocytes was experimentally modulated by exposure to antigen-antibody complexes. Mumps virions lacking both of their spike glycoproteins (HANA and F) failed to generate virus dependent cytotoxicity. Virions lacking only HANA also generated virus dependent cytotoxicity but their capacity to do so was markedly impaired. Solubilized preparations of viral spikes also enhanced cytotoxicity although to a lesser extent than intact virions. Anti-HANA antibodies, but not anti-F antibodies, abrogated cytotoxicity when incubated together with virus used for treatment of PBL. These experiments demonstrate that HANA was an essential component for the induction of cytotoxicity. The possible role of F remains to be established.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

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