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In contrast to most mouse lymph node cells, follicular dendritic cells (FDCs) resist cyclophosphamide (Cy)-mediated destruction in vivo. In this study researchers sought to determine if antigen-bearing FDCs from Cy-treated animals maintained biological activity. Researchers were especially interested in whether FDCs from Cy-treated animals could stimulate an antibody response when combined with primed spleen cells and whether the FDCs needed to be intact and viable for stimulation to occur. The effect of Cy treatment on lymph node histology, number of T cells and B cells and the "spontaneous antibody response" was determined.

Intratracheal instillation of sheep red blood cells (SRBC) induced a primary immune response in lung-associated lymph nodes of Chinese hamsters and Fischer-344 rats. Few or no anti-SRBC antibody forming cells (AFC) were found in the spleen or cervical lymph nodes after intratracheal immunization. The number of AFC was significantly suppressed in the lung-associated lymph nodes from hamsters exposed by inhalation of 239PuO2 and in rats exposed by intratracheal instillation of benzo(a)pyrene (BaP). Although the immunologic function of the lung-associated lymph nodes was suppressed by 239PuO2 and BaP exposure, there was no observable increase in the number of AFC in distant lymphoid tissues. These data indicate that damage to lung cells and/or cells in lung-associated lymph nodes can suppress immunity induced by deposition of antigen in the lung. Even though lung-associated lymph nodes in exposed animals contained lower numbers of AFC, antigen instilled into the lungs of exposed animals did not significatnly translocate to distant lymphoid tissues. This indicates that the antigen filtering capacity of the lung-associated lymph nodes was not altered.

This study describes the effect of intratracheal instillation of benzo(a)pyrene (BaP) on immunological responses in the lung-associated lymph nodes, cervical lymph nodes, and spleen after deposition of 10(8) sheep red blood cells (SRBC) in the lung or peritoneal cavity of rats. An increased number of anti-SRBC antibody-forming cells was observed in the lung-associated lymph nodes when rats were immunized simultaneously with BaP installation. A suppression in the number of anti-SRBC antibody-forming cells occurred when SRBC were given intratracheally 4 or 7 days after BaP. The effects of the BaP appeared to be on the function of the cells in the lung-associated lymph nodes rather than due to changes in the exposed lung. BaP-induced changes in antigen handling or in regulatory populations of immune cells in the lung-associated lymph nodes may be responsible for the immune alterations observed.

The effects of acute NO2 exposure on antigen-specific cell-mediated lung immunity in Fischer 344 rats were evaluated. Animals were exposed for 24 hr to either room air or 5, 10, or 26 ppm NO2 before intratracheal immunization with 10(8) sheep red blood cells (SRBC). Cellular immunity was evaluated by antigen-specific lymphocyte stimulation assays of pooled lymphoid cell suspensions from either the thoracic lymph nodes or spleens. Elevated cellular immunity was observed after exposure to NO2. The ability of the 26 ppm NO2 exposure to increase cellular immunity seemed to parallel, and in some cases even exceed, that seen in control animals immunized with SRBC mixed with 2 X 10(7) heat-killed Bacillus Calmette-Guerin. These results support the theory that lung damage, and/or alterations of regulatory populations of immune cells, induced by agents such as NO2 can be responsible for the production of abnormally elevated immune responses to antigens deposited in the damaged lung.

Our major objectives were to determine (1) when mice develop the cellular mechanisms necessary to trap and retain immune complexes in lymphoid follicles, (2) whether the ability to trap and retain immune complexes in lymphoid and collagenous tissues was maintained in old animals, and (3) whether the pattern of antigen localization in lymphoid follicles was altered as a consequence of ageing. Mice were passively immunized with a standardized amount of specific antibody and then challenged in the foot pads with radioactive antigen. The results indicated that newborn, and 1- and 2-week-old BALB/c mice lacked the cells or cellular mechanism necessary for trapping, localizing, and retaining immune complexes in lymphoid follicles. By 3 weeks, however, this ability to trap, retain, and localize antigen became apparent. The ability to trap and retain immune complexes on tendons and in lymphoid tissues was maintained as long as 27-30 months. A comparison of the quantity of antigen retained per mg of tissue in young-adult (6 months of age) and in old (27-30 months of age) mice indicated that old mice retained slightly more antigen in lymphoid tissues and substantially more on tendons. Antigen retained in spleens of both young-adult and old mice was localized in follicles by 24 h. However, the antigen retained in lymph nodes of old mice remained in the subcapsular sinus and adjacent superficial cortex and was not localized in follicles even after a full week. The cellular mechanisms necessary to trap and retain immune complexes in lymphoid tissue appear to develop in BALB/c mice a few weeks after birth and persist throughout life. However, localization of antigen in the lymphoid follicles of lymph nodes diminishes in old mice. The antigen trapping capability of collagenous tissues was not only maintained in old mice but was substantially increased.

A single intratracheal (i.t.) instillation of 3H-BaP (2.5 mg/kg) cleared rapidly from the lung with a half life of approximately 8 h. In contrast, the amount of 3H-BaP (expressed as counts/min/mg tissue) in the lung-associated lymph nodes (LALN) continued to increase over a 6 day period while a low, persistent level of BaP was detected in the spleen. To determine whether humoral immunity was affected by BaP accumulation in lymphoid organs, B6C3F1 mice were given seven daily i.t. instillations of 0.4, 4.0 or 40 mg BaP/kg, and immunized with sheep red blood cells (SRBC) 1 day after the last BaP instillation. When antigen was given by i.t. instillation, the number of antigen-specific, antibody-forming cells (AFC) decreased in the LALN after BaP exposure. Interestingly, the number of AFC in the LALN from BaP-exposed mice were significantly increased after intraperitoneal (i.p.) immunization. However, these same mice had lower numbers of AFC in the spleen. When 51Cr-SRBC were instilled in the lung, the pulmonary clearance of radiolabeled antigen was slowed in BaP-exposed mice. When 51Cr-SRBC were placed in the peritoneal cavity, the amount of radiolabeled antigen that reached the LALN was similar in BaP-exposed and vehicle mice. However, four times more radiolabeled antigen translocated from the peritoneal cavity to the lung in BaP-exposed mice, while significantly less antigen reached the spleen and liver. Thus, BaP-induced immunomodulation of the humoral immune response appears to be influenced by the route of immunization, as well as by the proximity of the responding lymphoid tissue to the site of BaP deposition.

This study describes immunologic response in lung-associated lymph nodes, spleen, cervical lymph nodes and lung lavage cells of rats immunized by intratracheal instillation of BCG-sheep red blood cell (SRBC) suspensions. At 4 through 17 days after immunization, the number of anti-SRBC IfM and IgG antibody-forming cells was significantly increased only in the lung-associated lymph nodes, indicating that these tissues retain the particulate antigen that was deposited in the lung. In contrast, cellular immunity was found initially in the spleen, with significant responses in the lungs and in the lung-associated lymph nodes on 13--19 days after immunization. Our data indicated that the lung-associated lymph nodes are probably the initial site for the production of antigen-sensitive lymphocytes for both antibody and cellular immunity after lung immunization. Cells responsible for cellular immunity appear to migrate to the spleen, where further cell division take place.

The objectives of this report are to explore known and potential regulatory roles of follicular dendritic cells (FDCs) in immune responses. FDCs are found in B-cell areas of lymphatic tissue and are especially rich around germinal centers where B-cell proliferation is occurring. Recent advances in isolating FDCs in our laboratories made it possible to begin investigating interactions of FDCs with other cells in vitro. In a series of experiments, we sought to determine whether a low concentration of FDC-enriched cells (2-10%) could enhance B-cell and/or T-cell mitogenesis. The results showed that an enriched population of FDCs markedly enhanced lipopolysaccharide-induced stimulation of nude mouse spleen cells, while an equivalent number of resident peritoneal cells or thymocytes had no effect. Depletion of Thy 1.2 positive cells or an exposure to 2400 rads of gamma radiation did not abrogate the enhancing capacity of FDC-enriched cells. FDC-enriched cells also increased phytohemagglutinin-induced proliferation. Scanning electron microscopy of FDC preparations showed that antigen-bearing dendritic processes of Type 2 FDCs have a "beaded" appearance. It was proposed that these immune complex coated microspheres may represent an important mechanism for exposing persisting antigen to the immune system. The gradual shedding of these microspheres may play an important role in regulating and maintaining immune responses within lymphoid tissues.