The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/3/1011/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 6, March 15, 1999 1011-1016

Brief Definitive Reports

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

Gregory D. Sempowski*, David M. Lee{ddagger}, Richard M. Scearce*, Dhavalkumar D. Patel*,{ddagger}, and Barton F. Haynes*,{ddagger}

From the * Division of Rheumatology, Allergy, and Clinical Immunology and the Department of Medicine; and the {ddagger} Department of Immunology and Duke University Arthritis Center, Duke University Medical Center, Durham, North Carolina 27710

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)-{gamma} production and CD8+ CTL generation. To determine the in vivo role of CD7 in systems dependent on IFN-{gamma}, 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-{gamma} and tumor necrosis factor (TNF)-{alpha} levels compared with control C57BL/6 mice (P < 0.001). Steady-state mRNA levels for IFN-{gamma} and TNF-{alpha} 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-{gamma} 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 x 105) versus C57BL/6 control mice (3.7 ± 0.8 x 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.

Key Words: CD7 • lipopolysaccharide • septic shock • NK1.1 • T cells

Address correspondence to Barton F. Haynes, Box 3703, Duke University Medical Center, Durham, NC 27710. Phone: 919-684-5384; Fax: 919-681-8992; E-mail: hayne002{at}mc.duke.edu


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