Impaired Clearance of Herpes Simplex Virus Type 1 From Mice Lacking CD1d or NKT Cells Expressing the Semivariant Vα14-Jα281 TCR

Abstract

Ag-presenting molecule CD1 and CD1-restricted NKT cells are known to contribute to defense against a range of infectious pathogens, including some viruses. CD1-restricted NKT cells, a distinct subpopulation of T cells, have striking and rapid effector functions that contribute to host defense, including rapid production of IFN-γ and IL-4, and activation of NK cells. Consideration of the important contributions of innate and adaptive immunity to clearance of HSV prompted us to investigate the role of CD1 and of NKT cells expressing the Vα14-Jα281 TCR in the pathogenesis of HSV infection. To address this issue, we compared infection in wild-type mice with that in CD1 gene knockout (GKO) and Jα281 GKO mice. In this study, we report impaired clearance of virus and viral Ags, and more florid acute infection in mice lacking CD1 (and by inference, CD1-restricted T cells), in comparison with parental C57BL6 mice. In Jα281 GKO mice there was also impairment of virus clearance, resembling that seen in CD1 GKO mice. These results imply roles for the Vα14-Jα281 subset of NKT cells and for CD1d in control of HSV infection.

Human Cytomegalovirus (HCMV) US2 Protein Interacts with Human CD1d (hCD1d) and Down-Regulates Invariant NKT (iNKT) Cell Activity

“…Several previous studies have demonstrated that the deficiency of iNKT cells leads to the greater susceptibility to certain viral infections (De Santo et al, 2008;Grubor-Bauk et al, 2003;Ilyinskii et al, 2006). These results were supported by the fact that animals with the stimulation of iNKT cells through CD1d pulsed with antigen (KRN 7000) were more resistance to specific viral infections Kakimi et al, 2000;van Dommelen et al, 2003).…”

“…The phenotype of CD1d-deficient mice is much more susceptible to different types of viral infection (De Santo et al, 2008;Grubor-Bauk et al, 2003;Ilyinskii et al, 2006). In addition, activation of iNKT cells by α-galactosylceramide (KRN 7000) through presentation by CD1d enhances the protection of host animals during several tested viral infections Kakimi et al, 2000;van Dommelen et al, 2003).…”

A Detrimental Role for Invariant Natural Killer T Cells in the Pathogenesis of Experimental Dengue Virus Infection

“…Several experimental models have highlighted the beneficial role of iNKT cells in virus-associated inflammatory responses. [27][28][29][30][31][32] However, they can also contribute to the immunopathogenesis of viral diseases. For example, using an experimental mouse model of chronic lung disease triggered by infection with Sendai virus, Kim et al 33 demonstrated that IL-13 production by iNKT cells contributes to pulmonary disease.…”

“…After comparison of the phenotypes of J␣18 Ϫ/Ϫ and wild-type (WT) animals, it was reported that the role of iNKT cells during experimental viral infection can vary according to the virus and experimental conditions. 20,24 -26 For example, during infection with influenza A virus, herpes simplex virus types 1 and 2, and lymphocytic choriomeningitis virus, iNKT cells have a positive role in anti-viral immune responses and virus-associated disease, [27][28][29][30][31][32] whereas during infection with Sendai virus and herpes simplex virus type 2 (only in aged mice), iNKT cells are rather deleterious. 33,34 However, iNKT cells do not seem to participate in anti-viral immunity or control of viral replication during infection with encephalomyocarditis virus and murine cytomegalovirus.…”

HSV Recombinant Vectors for Gene Therapy

“…iNKT cells are restricted to the monomorpic MHC class-I-like molecule CD1d for foreign and self-glycolipid antigens [284]. NKT cells are involved in the innate response to HSV in mice [302]. Recent studies confirmed the predominant role of NKT cells in controlling early viral replication and in determining mortality, neuroinvasion, loss of sensory neurons, lesions and level of latency [303].…”