All Phenotypes Copa<tm1.1Shum> MGI Mouse

lung inflammation ( J:288425 )

• mice show early, spontaneous inflammation with activation of cytokine-secreting CD4+ T cells

• however, mice do not develop appreciable erythema or swelling of the ankle, foot, or digits and there is absence of immune cell infiltration or cartilage loss in the joints

bronchiolitis ( J:288425 )

• lungs show cellular bronchiolitis with germinal center formation

• mononuclear cell infiltrates contain a predominance of CD4+ T cells and lymphoid aggregates comprised of B cells

abnormal lung morphology ( J:288425 )

• mice spontaneously develop interstitial lung disease that matches the lung pathologic condition in individuals with COPA syndrome

• lungs show a spectrum of acute and chronic lung damage ranging from mild to severe and include alveolar consolidation by edema, fibrin, proteinosis, and macrophage accumulation, type 2 pneumocyte hyperplasia and peribronchiolar inflammation with mixed infiltrates of lymphocytes that include Mott cells, vasculitis, lung fibrosis in areas of constrictive bronchiolitis

pulmonary edema ( J:288425 )

pulmonary alveolar proteinosis ( J:288425 )

reactive type II pneumocyte hyperplasia ( J:288425 )

pulmonary fibrosis ( J:288425 )

• lung fibrosis in areas of constrictive bronchiolitis

decreased double-positive T cell number ( J:288425 )

• the percentage of CD4+CD8+ double-positive cells is decreased

increased effector memory T-helper cell number ( J:288425 )

• mice show elevations in activated effector memory T cells

increased single-positive T cell number ( J:288425 )

• the percentages of CD4+ single-positive and CD8+ single-positive cells are increased

• increase in the percentages of TCRbeta+CD69+ and TCRbeta+CD69- single positive cells that arise postpositive selection

• the increased ratio of single-positive cells is caused by an increase in the single-positive cell population because double negative and double positive cell numbers are equivalent

• however, total cell numbers in thymi are normal in 4- and 6-week-old mice and numbers of double-negative T cells are normal

abnormal B cell morphology ( J:288425 )

• B cells show elevated levels of CD86 although serum IgG levels are not increased and no antinuclear autoantibodies, including autoantibodies to dsDNA or ribonuclear proteins are detected

• spleen shows no differences in total splenocytes, absolute numbers and percentages of B and T cells

abnormal T cell activation ( J:288425 )

• mice spontaneously develop activated, cytokine-secreting T cells; mice show a decrease in the percentage of CD44^loCD62L^hi naive CD4+ and CD8+ T cells and an increase in the percentages of activated CD44^hiCD62L^lo effector memory CD4+ and CD8+ T cells

• peripheral CD4+ and CD8+ T cells stimulated with PMA and ionomycin show an increase in IFN-gamma and IL-17A-secreting CD4+ T cells and IFN-gamma-secreting CD8+ T cells