The Role of Tissue Resident Memory CD4 T Cells in Herpes Simplex Viral and HIV Infection

Thomas R O'Neil; Kevin Hu; Naomi R Truong; Sana Arshad; Barbara L Shacklett; Anthony L Cunningham; Najla Nasr

doi:10.3390/v13030359

The Role of Tissue Resident Memory CD4 T Cells in Herpes Simplex Viral and HIV Infection

Viruses. 2021 Feb 25;13(3):359. doi: 10.3390/v13030359.

Authors

Thomas R O'Neil^{1

2}, Kevin Hu^{1

2}, Naomi R Truong^{1

2}, Sana Arshad^{1

2}, Barbara L Shacklett³, Anthony L Cunningham^{1

2}, Najla Nasr^{1

4}

Affiliations

¹ Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, NSW 2145, Australia.
² Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW 2145, Australia.
³ Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA 95616, USA.
⁴ School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2000, Australia.

Abstract

Tissue-resident memory T cells (TRM) were first described in 2009. While initially the major focus was on CD8⁺ TRM, there has recently been increased interest in defining the phenotype and the role of CD4⁺ TRM in diseases. Circulating CD4⁺ T cells seed CD4⁺ TRM, but there also appears to be an equilibrium between CD4⁺ TRM and blood CD4⁺ T cells. CD4⁺ TRM are more mobile than CD8⁺ TRM, usually localized deeper within the dermis/lamina propria and yet may exhibit synergy with CD8⁺ TRM in disease control. This has been demonstrated in herpes simplex infections in mice. In human recurrent herpes infections, both CD4⁺ and CD8⁺ TRM persisting between lesions may control asymptomatic shedding through interferon-gamma secretion, although this has been more clearly shown for CD8⁺ T cells. The exact role of the CD4⁺/CD8⁺ TRM axis in the trigeminal ganglia and/or cornea in controlling recurrent herpetic keratitis is unknown. In HIV, CD4⁺ TRM have now been shown to be a major target for productive and latent infection in the cervix. In HSV and HIV co-infections, CD4⁺ TRM persisting in the dermis support HIV replication. Further understanding of the role of CD4⁺ TRM and their induction by vaccines may help control sexual transmission by both viruses.

Keywords: HIV-1; HSV-1/2; immunity; infection; keratitis; tissue resident CD4+, CD8+, vaccines.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
CD4-Positive T-Lymphocytes / immunology*
Coinfection / immunology
Coinfection / virology
HIV Infections / immunology*
HIV Infections / virology
Herpes Simplex / immunology*
Herpes Simplex / virology
Humans
Immunologic Memory / immunology*