Herpes Stromal Keratitis: Erosion of Ocular Immune Privilege by Herpes Simplex Virus

Jared E Knickelbein; Kristine-Ann Buela; Robert L Hendricks

Disclosures

Future Virology. 2010;5(6):699-708. 

In This Article

Tregs in HSK

Tregs comprise a critical component of the immune system, which functions to suppress untoward immunity and is essential in the maintenance of immune homeostasis and self-tolerance. Tregs come in many forms, including those that express the CD8 transmembrane glycoprotein, as well as those that express the markers CD4, CD25 and Foxp3. The initial description of CD25+ Treg function emerged from studies demonstrating that depletion of CD25-expressing cells led to organ-specific autoimmune disease.[38] One mechanism by which Tregs perform their regulatory function is by the production of inhibitory cytokines, such as IL-10 and TGF-β.[39] In the setting of HSK, normal immunoprotective CD4 T cells are responsible for immunopathology in the specialized microenvironment of the cornea. Conceivably, this viral-induced immunopathology, such as autoimmune lesions, may be controlled by Tregs.

Initial Treg studies, in an HSK model, demonstrated that depleting Tregs with anti-CD25 antibody treatment before corneal infection with HSV-1 brings about more severe lesions, and that disease occurs at infectious doses of the virus that normally would not cause HSK.[40] These more severe lesions were also associated with larger CD4 T-cell infiltrates in the cornea, indicating that Tregs may control the development of lesions by limiting pathogenic T-cell migration into the inflamed cornea. In the same study, adoptive transfer of Tregs blunted the response of cotransferred naive or primed CD4+CD25 responder T cells following HSV-1 infection. This suggests that Tregs play a role in minimizing the extent of immunopathogenic CD4 T-cell induction. A more recent study showed that Tregs and IL-10 may function independently in regulating the severity of HSK lesions.[41] Furthermore, the adoptive transfer of in vitro-generated Foxp3+ Tregs decreased disease severity in a murine model of HSK.[42] Augmenting the regulatory function of Tregs represents a promising means to control viral-induced inflammatory disease.

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