SummaryThe contribution of T lymphocyte subpopulations to intrapulmonary and systemic resistance against an opportunistic strain of Cryptococcus neoformans was examined . It was found that C. neoformans was destroyed when introduced into the lungs of normal mice, but disseminated to the brains of mice treated with an antibody that depleted them of CD4+ T cells. Depletion of either CD8+ or CD4+ T cells impaired the ability of the host to clear the yeast from the lung. These results, together with the observation that CD8+ T cells accumulate in the lungs of CD4+ T cell-deficient mice, suggest that CD8+ T cells play an important role in resistance to C. neoformans infection acquired via the respiratory tract .
Sllmmar~The possible mechanisms by which CD4 + T cells prevent the dissemination of Cryptococcus neoformans from the primary site of infection in the respiratory tract were examined. It was found that even before fungicidal mechanisms are fully induced in the lungs, the host generates a CD4 + T cell-dependent inflammatory response that sequesters yeast within the pulmonary alveoli. This confinement is evident histopathologically and demonstrable objectively as a rapid decline in the ability to dislodge yeast from the lungs by bronchopulmonary lavage. One striking component of this response is the enclosure of cryptococci within multinucleated giant cells in granulomas. Studies in severe combined immunodeficient mice that were engrafted with selected lymphocyte subpopulations show that B cells, and hence anti-Cryptococcus antibodies, are not necessary for the CD4 + T cell-dependent responses that isolate and subsequently destroy this opportunistic pathogen in the lung parenchyma.
This study examined the capacity of BALB/c mice that had been depleted of T cell subpopulations to generate a protective immune response to Leishmania major. Thymectomized mice were depleted of either L3T4+ (CD4+) T lymphocytes, Ly2+ (CD8+) T lymphocytes, or both, by treatment with appropriate mAbs. It was found that susceptible mice were rendered resistant to Leishmania by an intravenous infusion of anti-L3T4 mAb. These mice generated an immune response that destroyed the parasite in the primary lesion and in visceral metastatic foci. CD4+ cell-depleted mice also acquired a capacity to mount a sustained delayed-type hypersensitivity (DTH) response to parasite antigens, indicating that DTH, per se, is not a disease-promoting mechanism in the susceptible murine host as has been suggested. Depleting BALB/c mice of CD8+, as well as CD4+ T cells, left them highly susceptible to Leishmania infection, thereby indicating that CD8+ lymphocytes are key protective cells. Our results can be interpreted as showing that the susceptibility of BALB/c mice is due to the generation of CD4+ cells that suppress either the generation or expression of CD8+ T cell-mediated antiLeishmania immunity.
Previously published studies of experimental cutaneous leishmaniasis in the mouse have relied almost exclusively on measuring changes in lesion size to follow the course of the infection. The purposes of the studies reported here were to develop a technique to quantitate the number of viable organisms in the tissues and to use the technique to follow the development and resolution of the primary infection as well as the development of acquired resistance to Leishmania tropica in a resistant (C3H/He) and a susceptible (BALB/c) mouse strain. It was found that individual L. tropica amastigotes derived from infected tissues would tranform to promastigotes and repeatedly divide to form discrete, countable colonies on rabbit blood agar. The plating efficiency was approximately 88%. Using the blood agar plating technique to quantitate the organism against time of the infection, we obtained data that suggest that acquired resistance develops in C3H/He mice earlier than is suggested by reduction in lesion size. In addition, although this resistance eliminates the parasites from the primary lesion in 10 weeks, 1,000 to 10,000 parasites persist for months in the lymph node draining the lesion site. In these studies, we found no evidence of acquired resistance in the susceptible BALB/c mice. The organism grows progressively, and the infection can disseminate to the spleen within 2 weeks. These studies illustrate the advantages of quantitating viable parasites in studies of immunity in cutaneous leishmaniasis.
The immune response in immunized and unimmunized bronchoalveolar spaces, as well as in the blood, was measured after localized deposition of antigen in the lung. Using a fiberoptic bronchoscope, groups of dogs were immunized with sheep red blood cells (SRBC) deposited into a single airway of the left apical or right apical lung lobes. Bronchoalveolar cells were obtained by lung lavage through the fiberoptic bronchoscope from the immunized lung lobe, as well as from lung lobes that did not receive antigen. Lavage cells and blood samples were collected at 3 to 21 days after immunization. The total number of lymphocytes, macrophages, and polymorphonuclear leukocytes, and the number of lymphoid cells producing anti-SRBC IgM and IgG antibodies were determined. Our results indicated that the highest number of antibody-forming cells (AFC) were found in the immunized lung lobes. An elevated, but significantly lower number of AFC were observed in the unimmunized lung lobes. The number of IgM and IgG AFC in the blood reached peak concentrations 3 to 7 days earlier than the AFC in the lung. We concluded from our data that the blood is an important source of the AFC found in the lung.
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