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J. Exp. Med.,
Volume 189, Number 6, March 15, 1999 1011-1016
By
From the * Division of Rheumatology, Allergy, and Clinical Immunology and the Department of
Medicine; and the 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)- Department of Immunology and Duke University Arthritis Center, Duke
University Medical Center, Durham, North Carolina 27710
production and CD8+ CTL generation. To determine
the in vivo role of CD7 in systems dependent on IFN-, 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- and tumor necrosis factor (TNF)-
levels
compared with control C57BL/6 mice (P < 0.001). Steady-state mRNA levels for IFN- and
TNF- 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- 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.
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