Absence of CD5 Dramatically Reduces Progression of Pulmonary Inflammatory Lesions in SHP-1 Protein-Tyrosine Phosphatase-Deficient ‘Viable Motheaten’ Mice
pmid: 11908943
Absence of CD5 Dramatically Reduces Progression of Pulmonary Inflammatory Lesions in SHP-1 Protein-Tyrosine Phosphatase-Deficient ‘Viable Motheaten’ Mice
Mice homozygous for the viable motheaten (Hcph(me-v)) mutation are deficient in SHP-1 protein-tyrosine phosphatase, resulting in severe systemic autoimmunity and immune dysfunction. A high percentage of B-cells in viable motheaten mice express the cell surface glycoprotein CD5, in contrast to wild type mice that express CD5 on only a small percentage of B-cells. CD5(+) B-cells have been associated with autoantibody production. To determine the role of CD5 in the development of the inflammatory disease in me(v)/ me(v) mice, we created a stock of CD5(null)me(v)/ me(v) mice. The longevity of CD5(null)me(v)/ me(v) mice was increased 69% in comparison to me(v)/ me(v) mice on a similar (B6;129) background. The increased lifespan was associated with a marked reduction in pulmonary inflammation. Flow cytometry analysis of spleen cells from CD5(null)me(v)/ me(v) mice at 9-12 weeks of age revealed significant decreases in percentages of IgM/B220 double positive B-cells, Mac-1/Gr-1 double positive cells and CD4(+) T-cells compared with me(v)/ me(v) mice. CD5(null)me(v)/ me(v) mice also had significantly lower serum IgM levels in comparison to me(v)/ me(v) mice. Study of CD5(null)me(v)/ me(v) mice may provide further insight into the role of CD5 in cell signaling and may help explain the observed association of CD5(+) B-cells with autoimmune disease.
- University of Connecticut United States
- Cleveland Clinic United States
- Jackson Laboratory United States
Male, Mice, Knockout, 570, Macrophages, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Longevity, Intracellular Signaling Peptides and Proteins, 610, Immunoglobulins, Bone Marrow Cells, Pneumonia, CD5 Antigens, Mice, Mutant Strains, Blood Cell Count, Mice, Inbred C57BL, Mice, Animals, Female, Protein Tyrosine Phosphatases, Spleen, Autoantibodies
Male, Mice, Knockout, 570, Macrophages, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Longevity, Intracellular Signaling Peptides and Proteins, 610, Immunoglobulins, Bone Marrow Cells, Pneumonia, CD5 Antigens, Mice, Mutant Strains, Blood Cell Count, Mice, Inbred C57BL, Mice, Animals, Female, Protein Tyrosine Phosphatases, Spleen, Autoantibodies
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