Background Genital mucosa is the main portal of entry for various incoming pathogens, including human immunodeficiency virus (HIV), hence it is an important site for host immune defenses. Tissue-resident memory T (T RM) cells defend tissue barriers against infections and are characterized by expression of CD103 and CD69. In this study, we describe the composition of CD8+ T RM cells in the ectocervix of healthy and HIV-infected women. Methods Study samples were collected from healthy Swedish and Kenyan HIV-infected and uninfected women. Customized computerized image-based in situ analysis was developed to assess the ectocervical biopsies. Genital mucosa and blood samples were assessed by flow cytometry. Results Although the ectocervical epithelium of healthy women was populated with bona fide CD8+ T RM cells (CD103 + CD69 +), women infected with HIV displayed a high frequency of CD103- CD8+ cells residing close to their epithelial basal membrane. Accumulation of CD103- CD8+ cells was associated with chemokine expression in the ectocervix and HIV viral load. CD103 + CD8+ and CD103- CD8+ T cells expressed cytotoxic effector molecules in the ectocervical epithelium of healthy and HIV-infected women. In addition, women infected with HIV had decreased frequencies of circulating CD103 + CD8+ T cells. Conclusions Our data provide insight into the distribution of CD8+ T RM cells in human genital mucosa, a critically important location for immune defense against pathogens, including HIV.

Human immunodeficiency virus-infected women have high numbers of CD103- CD8+ T Cells Residing Close to the Basal Membrane of the Ectocervical Epithelium / A. Gibbs, M. Buggert, G. Edfeldt, P. Ranefall, A. Introini, S. Cheuk, E. Martini, L. Eidsmo, T.B. Ball, J. Kimani, R. Kaul, A.C. Karlsson, C. Wahlby, K. Broliden, A. Tjernlund. - In: THE JOURNAL OF INFECTIOUS DISEASES. - ISSN 0022-1899. - 218:3(2018), pp. 453-465. [10.1093/infdis/jix661]

Human immunodeficiency virus-infected women have high numbers of CD103- CD8+ T Cells Residing Close to the Basal Membrane of the Ectocervical Epithelium

A. Introini;
2018

Abstract

Background Genital mucosa is the main portal of entry for various incoming pathogens, including human immunodeficiency virus (HIV), hence it is an important site for host immune defenses. Tissue-resident memory T (T RM) cells defend tissue barriers against infections and are characterized by expression of CD103 and CD69. In this study, we describe the composition of CD8+ T RM cells in the ectocervix of healthy and HIV-infected women. Methods Study samples were collected from healthy Swedish and Kenyan HIV-infected and uninfected women. Customized computerized image-based in situ analysis was developed to assess the ectocervical biopsies. Genital mucosa and blood samples were assessed by flow cytometry. Results Although the ectocervical epithelium of healthy women was populated with bona fide CD8+ T RM cells (CD103 + CD69 +), women infected with HIV displayed a high frequency of CD103- CD8+ cells residing close to their epithelial basal membrane. Accumulation of CD103- CD8+ cells was associated with chemokine expression in the ectocervix and HIV viral load. CD103 + CD8+ and CD103- CD8+ T cells expressed cytotoxic effector molecules in the ectocervical epithelium of healthy and HIV-infected women. In addition, women infected with HIV had decreased frequencies of circulating CD103 + CD8+ T cells. Conclusions Our data provide insight into the distribution of CD8+ T RM cells in human genital mucosa, a critically important location for immune defense against pathogens, including HIV.
CD8; +; T RM; genital mucosa; HIV; imaging analysis; in situ; Adult; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Basement Membrane; Biopsy; CD8-Positive T-Lymphocytes; Cervix Uteri; Female; Flow Cytometry; HIV Infections; Healthy Volunteers; Humans; Integrin alpha Chains; Kenya; Lectins, C-Type; Middle Aged; Mucous Membrane; Sweden; T-Lymphocyte Subsets; Young Adult
Settore MED/04 - Patologia Generale
Settore MED/50 - Scienze Tecniche Mediche Applicate
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/871279
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