Experimental data already obtained in this project demonstrate a deficiency in the ability of unprimed lung tissue to manifest immune responses to local immunization in vivo and a reduced ability of pulmonary lymphoid cells to respond to immune stimulation in vitro. The overall objective of this research proposal is to elucidate the mechanisms responsible for the reduced responses of pulmonary lymphoid cells to immune stimulation in vivo and in vitro. The adequacy of the composition of pulmonary lymphoid cells will be defined by determining whether antigen-reactive B and T lymphocytes, appropriate for generation of anti-body-forming cells, are present normally in murine lungs and by determining whether murine alveolar macrophages are capable of processing antigen for immune responses. Suppressive factors which may be operative in the lung will be defined by determining the mechanism by which murine alveolar macrophages inhibit the generation of antibody-forming cells in vitro and the mechanism by which canine alveolar macrophages suppress lymphocyte responses to mitogens. The innate immune reactivity of pulmonary lymphocytes will be defined by determining whether the reduced proliferative responses of canine bronchoalveolar lymphocytes is due to abnormalities in immune recognition or abnormalities in proliferative events preceding DNA synthesis. These studies are expected to provide information which increases our understanding of factors regulating immune reactivity of normal lungs and may provide insight into factors contributing to the pathogenesis of immunologic lung disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL034298-13
Application #
3347070
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1984-12-01
Project End
1988-06-30
Budget Start
1986-12-01
Budget End
1988-06-30
Support Year
13
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Beck, J M; Warnock, M L; Kaltreider, H B et al. (1993) Host defenses against Pneumocystis carinii in mice selectively depleted of CD4+ lymphocytes. Chest 103:116S-118S
Kaltreider, H B (1993) Hypersensitivity pneumonitis. West J Med 159:570-8
Curtis, J L; Byrd, P K; Warnock, M L et al. (1993) Pulmonary lymphocyte recruitment: depletion of CD8+ T cells does not impair the pulmonary immune response to intratracheal antigen. Am J Respir Cell Mol Biol 9:90-8
Curtis, J L; Byrd, P K; Warnock, M L et al. (1991) Requirement of CD4-positive T cells for cellular recruitment to the lungs of mice in response to a particulate intratracheal antigen. J Clin Invest 88:1244-54
Beck, J M; Warnock, M L; Curtis, J L et al. (1991) Inflammatory responses to Pneumocystis carinii in mice selectively depleted of helper T lymphocytes. Am J Respir Cell Mol Biol 5:186-97
Curtis, J L; Warnock, M L; Arraj, S M et al. (1990) Histologic analysis of an immune response in the lung parenchyma of mice. Angiopathy accompanies inflammatory cell influx. Am J Pathol 137:689-99
Curtis, J L; Kaltreider, H B (1989) Characterization of bronchoalveolar lymphocytes during a specific antibody-forming cell response in the lungs of mice. Am Rev Respir Dis 139:393-400
Kaltreider, H B; Byrd, P K; Curtis, J L (1988) Expression of Ia by murine alveolar macrophages is upregulated during the evolution of a specific immune response in pulmonary parenchyma. Am Rev Respir Dis 137:1411-6
Kaltreider, H B; Curtis, J L; Arraj, S M (1987) The mechanism of appearance of specific antibody-forming cells in lungs of inbred mice after immunization with sheep erythrocytes intratracheally. II. Dose-dependence and kinetics of appearance of antibody-forming cells in hilar lymph nodes and lungs of u Am Rev Respir Dis 135:87-92
Kaltreider, H B; Caldwell, J L; Byrd, P K (1986) The capacity of normal murine alveolar macrophages to function as antigen-presenting cells for the initiation of primary antibody-forming cell responses to sheep erythrocytes in vitro. Am Rev Respir Dis 133:1097-104

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