title: Intravaginal infection with herpes simplex virus type-2 (HSV-2) generates a functional effector memory T cell population that persists in the murine genital tract.
abstract: Although the female genital tract is the main portal of entry for sexually transmitted infections in women, we still have limited understanding of the generation, maintenance and characteristics of memory T cells in the local tissue. Here, we utilized a mouse model of intravaginal HSV-2 infection and tetramers against the immunodominant HSV glycoprotein B epitope recognized by CD8+ T cells to examine the generation, maintenance and characteristics of anti-HSV memory T cells in the genital tract following acute infection. Our results show that the highest percentage of HSVgB-specific CD8+ T cells was found in the genital tract compared to the spleen or iliac lymphnode. Indeed, although the actual number of CD8+ T cells contracted following viral clearance, approximately one quarter of the CD8+ population that remained in the genital tissue was HSVgB-specific. Memory gB-tetramer+CD8 T cells in the genital tract were positive for CD127 and KLRG1 and negative for CD62L and CCR7, thus confirming that HSV-specific CD8 cells were effector memory T cells that lack the capacity for homing to lymphoid tissues. Functionally, both memory CD8+ and CD4+ HSV-specific populations in the genital tract produced IFNγ when stimulated in vitro and CD4+ cells also produced TNFα. Genital HSVgB-specific memory T cells expressed tissue-homing integrins CD103 (αE integrin) and CD49a (VLA-1 or α1 integrin). Our findings suggest that HSV-specific memory T cells are retained in the genital tract, poised to act as an early line of defense against future virus encounter.
authors.affiliation: Michael G. DeGroote Institute for Infectious Disease Research, Department of Pathology & Molecular Medicine, McMaster University, MDCL 4019, 1200 Main St. West, Hamilton, Ontario, Canada.
authors.forename: Vera A
authors.initials: VA
authors.lastname: Tang
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Rosenthal
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005836:Genitalia, Female / Q000276:immunology* / Q000821:virology; D006558:Herpes Genitalis / Q000276:immunology* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000276:immunology*; D007156:Immunologic Memory; D039001:Integrin alpha Chains / Q000096:biosynthesis; D039423:Integrin alpha1 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D039001:Integrin alpha Chains; D039423:Integrin alpha1; D053699:Interleukin-7 Receptor alpha Subunit; C113413:KLRG1 protein, human; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D014759:Viral Envelope Proteins; C091367:alpha E integrins; C044525:glycoprotein B, herpes simplex virus type 2; D007371:Interferon-gamma