Earlier reports in this series (1, 2) focused upon the cytokinetics and properties of the specifically sensitized lymphocytes which collaborate with macrophages in host resistance to Listeria monocytogenes. Evidence was obtained that the sensitized lymphocytes are generated in animals primarily immunized with the living organism. As a population, they have a rapid turnover, short effective life-span, and fail to recirculate efficiently from the blood to lymph. These and other findings imply that immunoblasts or "large lymphocytes" are the principal, although possibly not the exclusive, specific effector cells responsible for transferring resistance to L. monocytogenes, at least in the rat.Several lines of evidence indicate that specifically sensitized lymphocytes collaborate with macrophages in the expression of cellular resistance to infection (3, 4). Although the mechanism underlying their collaboration has not yet been determined, it is plausible to think that meaningful interactions occur locally in foci of infection. It may be significant therefore that after intravenous injection into rats, immunoblasts from the thoracic duct lymph of Listeriainfected donors localize in substantial numbers in inflammatory exudates induced in the peritoneal cavity (5). The results of the current investigation reaffirm and extend this observation by showing that immunoblasts move from the blood into bacteria-induced exudates in a functionally active condition and for reasons other than their immunological commitment. In addition, they indicate that the immigrant cells and small lymphocytes derived from them have protective properties. Materials and MethodsAnimals.--The subjects of this study were male and female (Lewis X DA) Fx hybrid rats. Cell donors weighed 180--240 g. The recipients fell into two groups with respect to body weight: rats in whom antimicrobial resistance was measured weighed 70--100g, whereas those given radioactively labeled ceils were approximately the same weight as the donors.
Newcastle disease virus (NDV) can interact in at least two ways with rat T cells. By adsorbing to circulating lymphocytes, the virus can transiently deflect the cells from lymph nodes and inflammatory exudates induced in the peritoneal cavity. T cells are affected regardless of age, state of activation, or position in the mitotic cycle. The effect is reversible and is mediated not only by infectious (I)-NDV, but also by UV-NDV which cannot achieve a complete replication cycle in eggs. But I-NDV has another lasting effect on activated T cells. It is revealed in the failure of virus-treated thoracic duct lymphocytes to transfer cellular resistance to Listeria monocytogenes, delayed-type hypersensitivity to soluble antigens of the parasite, and the permanent exclusion of labeled S-phase lymphocytes from inflammatory foci. Activated T cells are inhibited by virus multiplicites which have little if any effect upon the proliferative potential of antigen-sensitive T cells or localization of labeled small lymphocytes in lymph nodes. The underlying mechanism has not been determined; however, there are reasons for thinking that NDV has a lethal effect upon activated T cells, because the latter are permissive for virus replication.
Bacterial parasites that can survive and multiply intracellularly are notable for their ability to induce delayed-type hypersensitivity and a concomitant state of resistance that is expressed in the enhanced capacity of macrophages to kill ingested organisms (1). The mechanism by which macrophages become activated in this respect has not been determined, but the process clearly involves an activity of specifically sensitized lymphocytes. These are formed in the infected animal and can be detected by their ability to protect recipients against the homologous parasite.Cells that can protect normal rats against a challenge infection with Listeria monocylogenes (2) or Mycobacterium tuberculosis (Lefford, McGregor, and Mackaness, unpublished data) are delivered to the thoracic duct of donors infected with these organisms. The appearance of protective cells in the 15mph of Lisleria-infected subjects coincides with the influx of many newly formed lymphocytes: large, medium, and small (2). If the protective cells belong to a rapidly proliferating cell population, as the foregoing observation suggests, they should be vulnerable to agents that inhibit cell replication. Support for this notion was obtained in the current investigation in which the plant alkaloid vinblastine sulfate (Vbl) ~ was used to analyze the part played by dividing and nondividing lymphocytes in the transfer of cellular resistance to infection.It will be shown that a single injection of Vbl given to rats at the peak of their response to a primary infection with L. monocytogenes deletes specifically sensitized effector cells from the thoracic duct and from an inflammatory exudate induced in the peritoneal cavity. The results point to dividing (large) lymphocytes as the specific mediators of host resistance to L. monocytogenes and provide a plausible explanation for their rapid turnover and short circulating life-span (2).
Mice immunized with 108 live Mycobacterium lepraemurium in the footpad showed increased resistance to infection with BCG or M. tuberculosis RlRv. This resistance could be transferred adoptively with lymphoid cells, signifying that the immunity was cross-reactive rather than nonspecific. Adoptive cross-reactive immunity to M. tuberculosis was also conferred by spleen cells from mice immunized with large doses of living or dead M. lepraemurium intravenously, a route of immunization that suppresses the induction of cell-mediated immunity to that organism. The presence of specific suppressor activity was sought in mice immunized intravenously with M. lepraemurium. It was found that mice preimmunized intravenously with living or dead M. lepraemurium and then infected with BCG did not confer levels of adoptive antituberculosis immunity as high as those conferred by mice immunized with BCG alone. Similarly, a mixture of BCG-sensitized and M. lepraemurium-sensitized cells did not convey as much immunity as BCG-sensitized cells alone, signifying suppression of the effector lymphocytes.in a volume of 0.04 ml or i.v. in a volume of 0.2 ml. Lymphoid cells were injected i.v.Lymphoid cells. Spleens, popliteal lymph nodes (PLN), or mesenteric lymph nodes (MLN) were re-1023 on August 1, 2020 by guest http://iai.asm.org/ Downloaded from
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