David A. Armstrong

Cutting Edge: The T Cell Chemoattractant IFN-Inducible Protein 10 Is Essential in Host Defense Against Viral-Induced Neurologic Disease

The contribution of the T cell chemoattractant chemokine IFN-inducible protein 10 (IP-10) in host defense following viral infection of the CNS was examined. IP-10 is expressed by astrocytes during acute encephalomyelitis in mouse hepatitis virus-infected mice, and the majority of T lymphocytes infiltrating into the CNS expressed the IP-10 receptor CXCR3. Treatment of mice with anti-IP-10 antisera led to increased mortality and delayed viral clearance from the CNS as compared with control mice. Further, administration of anti-IP-10 led to a >70% reduction (p ≤ 0.001) in CD4+ and CD8+ T lymphocyte infiltration into the CNS, which correlated with decreased (p ≤ 0.01) levels of IFN-γ. These data indicate that IP-10 functions as a sentinel molecule in host defense and is essential in the development of a protective Th1 response against viral infection of the CNS.

Expression of Mig (Monokine Induced by Interferon-γ) Is Important in T Lymphocyte Recruitment and Host Defense Following Viral Infection of the Central Nervous System

Induction of a Th1 immune response against viral infection of the CNS is important in contributing to viral clearance. The present studies demonstrate a role for the T cell chemoattractant chemokine Mig (monokine induced by IFN-γ) in contributing to a Th1 response against mouse hepatitis virus infection of the CNS. Analysis of the kinetics of Mig expression revealed mRNA transcripts present at days 7 and 12 postinfection (p.i.) but not early (day 2) or late (day 35) in the infection. To determine functional significance, mouse hepatitis virus-infected mice were treated with anti-Mig antisera, and the severity of disease was evaluated. Such treatment resulted in a marked increase in mortality that correlated with a >3 log increase in viral burden within the brains as compared with control mice treated with normal rabbit serum. Anti-Mig-treated mice displayed a significant decrease (p < 0.005) in CD4+ and CD8+ T cell recruitment into the CNS as compared with normal rabbit serum-treated mice. In addition, anti-Mig treatment resulted in a significant decrease (p < 0.05) in levels of IFN-γ and IFN-β that coincided with increased (p < 0.02) expression of the anti-inflammatory Th2 cytokine IL-10 within the CNS. Collectively, these data indicate that Mig is important in contributing to host defense by promoting a protective Th1 response against viral infection of the CNS.

Experimental wound repair in the black abalone, Haliotis cracherodii☆

Histological sections of incisions made in the mantle and foot of the black abalone, Haliotis cracherodii, revealed a number of differences in wound healing of the two tissues. Initial muscular closure of the wound was more pronounced in the mantle as was invagination of the cut edges. Within 8 hr post-incision, leukocytes lined the wound surface, initiating granulation tissue formation. A layer of squamous epithelium covered this reparative tissue in the wound cavity within 16 days. Leukocytes and collagen deposition filled the foot wound cavity, pushing the new epithelium upward until it was even with the normal epithelial surface. Mucous cell secretion indicated that the new epithelium was functional 2 months after incision. Granulation tissue did not fill up the mantle wound cavity, so that the epithelial surface was still depressed 75 days post-incision. Granulation tissue formation in the foot was far more elaborate than that of the mantle during all phases of wound healing. In both structures epithelial differentation and vascularization of the granulation tissue occurred within 2 months after incision. Muscle development in the healing wound appeared to result from new muscle formation within the granulation tissue rather than by gradual infiltration of muscle fibers from the surrounding tissue. The healed tissue in both structures appeared to be functional.

The CXC chemokines IP-10 and Mig are essential in host defense following infection with a neurotropic coronavirus.

Chemokines represent an ever-growing family of secreted proteins that function as potent mediators of inflammation (for review, see Luster, 1998). These molecules have been classified depending on the number and spacing of the first two conserved amino terminal cysteine residues into the C, CC, CXC, and CX3C family. Studies have shown that chemokines target specific leukocyte populations during periods of inflammation (Luster, 1998; Lane et al., 2000; Biddison et al., 1998; Kolb et al, 1999). In addition, chemokines have been shown to be prominently expressed following viral infection of the CNS (Lane et al, 1998; Cheret et al., 1997, Asensio and Campbell, 1997; Hoffman et al., 1999). However, the functional significance of chemokine expression within this environment has not been fully defined.