Recent advances in human kidney transplantation have brought the need for a more careful analysis and understanding of histocompatibility in man. The results of human renal allografting indicate that although parents or siblings are the best donors, grafts from unrelated donors occasionally survive for prolonged periods (1), presumably due to chance compatibility. A means for measuring histocompatibility in man is, therefore, needed. To this end, a number of experimental approaches have been proposed, namely leukoagglutination (2-4) and lymphocytotoxic serotyping (5, 6) of tissue antigens; interaction of allogeneic lymphocytes in vitro (7-9); cross reactions in skin transplantation, the so-called third man test ( 10); skin reactions produced by lymphocytes in irradiated hamsters (11); and the normal lymphocyte transfer reaction (NLT). This latter phenomenon, described by Brent and Medawar (12) in the guinea pig, is a result of the transfer of viable peripheral blood lymphocytes from one individual to an intradermal site in another individual. The immunologically competent cells are presumably able to react in a graft vs. host fashion against the histocompatibility antigens in the dermis of the cell recipient, forming a reaction that is expressed as an inflammatory nodule in the skin, reaching its peak approximately 48 hours after inoculation. In the guinea pig the intensity of the reaction was shown to cor-
Influenza antigens inoculated into the lung induce local immune responses. It has been proposed that this induction might be partly regulated by local antigen-presenting cells. The purpose of the current study was to inoculate heat-inactivated influenza virus into the tracheae of guinea pigs and determine the quantity of antigens that became cell-associated. Second, we determined how long antigen-presenting bronchoalveolar cells that had taken up virus in vivo retained their ability to specifically stimulate virus-immune T lymphocytes. Radioiodinated heat-inactivated influenza virus was inoculated into the tracheae of guinea pigs. The animals were killed from 30 min to 14 days after intratracheal inoculation, and radioactivity was determined in cells isolated from lung tissue. At least one-third of the radioactivity in the lungs was cell-associated from 1 to 14 days post-inoculation. In separate studies, heat-inactivated virus was inoculated into the airways of guinea pigs, and animals were killed at various times thereafter. Bronchoalveolar cells from these animals were compared with those from uninoculated controls in their ability to specifically stimulate virus-immune T cells to proliferate in vitro. Bronchoalveolar cells from virus-inoculated animals specifically stimulated T lymphocytes for up to 7 days after virus inoculation. These studies suggest that immunogenic virus persists in the lung within antigen-presenting cells for at least 1 week and possibly for up to 2 weeks. The persisting immunogenic stimulus after the termination of viral infections might be critical in ensuring the development of a local protective immune response.
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