Resistance of CD7-deficient Mice to Lipopolysaccharide-induced Shock Syndromes

CD7 is an immunoglobulin superfamily molecule involved in T and natural killer (NK) cell activation and cytokine production. CD7-deficient animals develop normally but have antigen-specific defects in interferon (IFN)-γ production and CD8⁺ CTL generation. To determine the in vivo role of CD7 in systems dependent on IFN-γ, the response of CD7-deficient mice to lipopolysaccharide (LPS)-induced shock syndromes was studied. In the high-dose LPS-induced shock model, 67% of CD7-deficient mice survived LPS injection, whereas 19% of control C57BL/6 mice survived LPS challenge (P < 0.001). CD7-deficient or C57BL/6 control mice were next injected with low-dose LPS (1 μg plus 8 mg D-galactosamine [D-gal] per mouse) and monitored for survival. All CD7-deficient mice were alive 72 h after injection of LPS compared with 20% of C57BL/6 control mice (P < 0.001). After injection of LPS and D-gal, CD7-deficient mice had decreased serum IFN-γ and tumor necrosis factor (TNF)-α levels compared with control C57BL/6 mice (P < 0.001). Steady-state mRNA levels for IFN-γ and TNF-α in liver tissue were also significantly decreased in CD7-deficient mice compared with controls (P < 0.05). In contrast, CD7-deficient animals had normal liver interleukin (IL)-12, IL-18, and interleukin 1 converting enzyme (ICE) mRNA levels, and CD7-deficient splenocytes had normal IFN-γ responses when stimulated with IL-12 and IL-18 in vitro. NK1.1⁺/ CD3⁺ T cells are known to be key effector cells in the pathogenesis of toxic shock. Phenotypic analysis of liver mononuclear cells revealed that CD7-deficient mice had fewer numbers of liver NK1.1⁺/CD3⁺ T cells (1.5 ± 0.3 × 10⁵) versus C57BL/6 control mice (3.7 ± 0.8 × 10⁵; P < 0.05), whereas numbers of liver NK1.1⁺/CD3⁻ NK cells were not different from controls. Thus, targeted disruption of CD7 leads to a selective deficiency of liver NK1.1⁺/ CD3⁺ T cells, and is associated with resistance to LPS shock. These data suggest that CD7 is a key molecule in the inflammatory response leading to LPS-induced shock.