Absence of CD5 dramatically reduces progression of pulmonary inflammatory lesions in SHP-1 protein-tyrosine phosphatase-deficient 'viable motheaten' mice

Abstract

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.