scholarly journals Identification and Characterization of Herpes Simplex Virus‐Specific CD4+T Cells in Corneas of Herpetic Stromal Keratitis Patients

1998 ◽  
Vol 177 (2) ◽  
pp. 484-488 ◽  
Author(s):  
Georges M. G. M. Verjans ◽  
Lies Remeijer ◽  
Robert S. van Binnendijk ◽  
José G. C. Cornelissen ◽  
Hennie J. Völker‐Dieben ◽  
...  
Keyword(s):  
T Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cd4 T Cells ◽  
Herpetic Stromal Keratitis ◽  
Stromal Keratitis ◽  
Simplex Virus ◽  
Identification And Characterization

Characterization of herpes simplex virus (HSV) specific T cells isolated from corneas of patients with herpetic stromal keratitis

1997 ◽  
Vol 56 ◽  
pp. 22-23
Author(s):  
G.M.G.M. Verjans ◽  
L. Remeijer ◽  
R.S. van Binnendijk ◽  
J. Cornelissen ◽  
H.J. Völker-Dieben ◽  
...  
Keyword(s):  
T Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Herpetic Stromal Keratitis ◽  
Stromal Keratitis ◽  
Simplex Virus

scholarly journals Dendritic Cell Autophagy Contributes to Herpes Simplex Virus-Driven Stromal Keratitis and Immunopathology

mBio ◽  
2015 ◽  
Vol 6 (6) ◽  
Author(s):  
Yike Jiang ◽  
Xiaotang Yin ◽  
Patrick M. Stuart ◽  
David A. Leib
Keyword(s):  
T Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Dendritic Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Herpetic Stromal Keratitis ◽  
Stromal Keratitis ◽  
Simplex Virus

ABSTRACTHerpetic stromal keratitis (HSK) is a blinding ocular disease that is initiated by HSV-1 and characterized by chronic inflammation in the cornea. Although HSK immunopathology of the cornea is well documented in animal models, events preceding this abnormal inflammatory cascade are poorly understood. In this study, we have examined the activation of pathological CD4+T cells in the development of HSK. Dendritic cell autophagy (DC-autophagy) is an important pathway regulating major histocompatibility complex class II (MHCII)-dependent antigen presentation and proper CD4+T cell activation during infectious diseases. Using DC-autophagy-deficient mice, we found that DC-autophagy significantly and specifically contributes to HSK disease without impacting early innate immune infiltration, viral clearance, or host survival. Instead, the observed phenotype was attributable to the abrogated activation of CD4+T cells and reduced inflammation in HSK lesions. We conclude that DC-autophagy is an important contributor to primary HSK immunopathology upstream of CD4+T cell activation.IMPORTANCEHerpetic stromal keratitis (HSK) is the leading cause of infectious blindness in the United States and a rising cause worldwide. HSK is induced by herpes simplex virus 1 but is considered a disease of inappropriately sustained inflammation driven by CD4+T cells. In this study, we investigated whether pathways preceding CD4+T cell activation affect disease outcome. We found that autophagy in dendritic cells significantly contributed to the incidence of HSK. Dendritic cell autophagy did not alter immune control of the virus or neurological disease but specifically augmented CD4+T cell activation and pathological corneal inflammation. This study broadens our understanding of the immunopathology that drives HSK and implicates the autophagy pathway as a new target for therapeutic intervention against this incurable form of infectious blindness.

scholarly journals CD28 Costimulation Is Required for Development of Herpetic Stromal Keratitis but Does Not Prevent Establishment of Latency

2019 ◽  
Vol 93 (16) ◽  
Author(s):  
Xiao-Tang Yin ◽  
Nicholas K. Baugnon ◽  
Chloe A. Potter ◽  
Shannon Tai ◽  
Tammie L. Keadle ◽  
...  
Keyword(s):  
T Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Wild Type ◽  
Corneal Disease ◽  
Herpetic Stromal Keratitis ◽  
Cd28 Costimulation ◽  
Stromal Keratitis ◽  
Simplex Virus

ABSTRACTCorneal infection with herpes simplex virus 1 (HSV-1) leads to infection of trigeminal ganglia (TG), typically followed by the establishment of latency in the infected neurons. When latency is disrupted, the virus reactivates and migrates back to the cornea, where it restimulates the immune response, leading to lesions in a disease called herpetic stromal keratitis (HSK). HSK requires T cell activation, as in the absence of T cells there is no disease. We decided to determine if CD28 costimulation of T cells was required in HSK. The results indicated that C57BL/6 CD28−/−and BALB/c CD28−/−mice failed to develop recurrent HSK, while their wild-type counterparts did. In order to better understand the dynamics of TG infection in these mice, we evaluated the amount of virus in infected TG and the number of individual neurons harboring latent virus. The results indicated that CD28−/−mice possessed significantly increased genome levels in their TG but many fewer LAT-positive cells than wild-type mice from day 7 to day 30 but that after day 30 these differences became nonsignificant. We next evaluated total and antigen-specific CD8+T cells in TG. The results indicated that there were significantly fewer CD8 T cells in TG from day 10 to day 25 but that after that the differences were not significant. Taken together, these data suggest that CD28 costimulation is required for HSK but that while initial infection of TG is greater in CD28−/−mice, this begins to normalize with time and this normalization is concurrent with the delayed development of antigen-specific CD8+T cells.IMPORTANCEWe study the pathogenesis of herpes simplex virus-mediated corneal disease. T cells play a critical role both in disease and in the maintenance of latency in neurons. Consequently, the focus of this study was to evaluate the role that T cell costimulation plays both in corneal disease and in controlling the ability of the virus to maintain a stable infection of the ganglia that innervate the cornea. We demonstrate that in the absence of costimulation with CD28, corneal disease does not take place. However, this costimulation does not prevent the ability of CD8+T cells to develop and, thus, control latent infection of neurons. We conclude from these studies that CD28 costimulation is required for corneal destructive immune responses but that CD8+T cells develop over time and help to maintain latency.

scholarly journals Innate Immune Responses to Herpes Simplex Virus Type 2 Influence Skin Homing Molecule Expression by Memory CD4+ Lymphocytes

2006 ◽  
Vol 80 (6) ◽  
pp. 2863-2872 ◽  
Author(s):  
David M. Koelle ◽  
Jay Huang ◽  
Michael T. Hensel ◽  
Christopher L. McClurkan
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cd4 T Cells ◽  
Receptor Expression ◽  
Homing Receptor ◽  
Skin Homing ◽  
Simplex Virus

ABSTRACT Herpes simplex virus (HSV) infections of humans are characterized by intermittent, lytic replication in epithelia. Circulating HSV-specific CD4 T cells express lower levels of preformed cutaneous lymphocyte-associated antigen (CLA), a skin-homing receptor, than do circulating HSV-specific CD8 T cells but, paradoxically, move into infected skin earlier than CD8 cells. Memory CD4 T cells develop strong and selective expression of CLA and E-selectin ligand while responding to HSV antigen in vitro. We now show that interleukin-12, type I interferon, and transforming growth factor beta are each involved in CLA expression by memory HSV type 2 (HSV-2)-specific CD4 T cells in peripheral blood mononuclear cells (PBMC). A reduction of the number of monocytes and dendritic cells from PBMC reduces CLA expression by HSV-2-responsive CD4 lymphoblasts, while their reintroduction restores this phenotype, identifying these cells as possible sources of CLA-promoting cytokines. Plasmacytoid dendritic cells are particularly potent inducers of CLA on HSV-reactive CD4 T cells. These observations are consistent with cooperation between innate and acquired immunity to promote a pattern of homing receptor expression that is physiologically appropriate for trafficking to infected tissues.

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