Peripheral blood lymphocytes from low-grade squamous intraepithelial lesions patients recognize vaccine antigens in the presence of activated dendritic cells, and produced high levels of CD8 + IFNγ + T cells and low levels of IL-2 when induced to proliferate (original) (raw)
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Folia Microbiologica, 1999
T(CD3+)-, B(CD19+)-lymphocytes and their subsets (CD4 +, CD8 +, CD3 + DR +, CD3-DR +) in peripheral blood of patients with CIN I, CIN II, CIN III and cancer in situ associated with HPV infection were evaluated. In peripheral blood of women with CIN II, CIN III and cancer in situ the number of T-lymphoeytes which expressed CD3 + DR + antigen decreased. In patients with CIN I, CIN III and cancer in situ the level of the CD4 + cells decreased; the level of the CD8 + ceils increased. These patients had a lower CD4/CD8 ratio, the number of B cells being standard. The results may have important implications in the prognosis and immunotherapy of HPV infection.
Cancer Cell International, 2014
Background: In response to antigen naive CD8+, T cells differentiate into effector cells, which express Natural killer (NK) receptors, lose CD28 expression, and die by apoptosis. However, in smaller quantities, the cells are retained for subsequent exposure to the same antigen. Knowledge is limited regarding whether the percentages of CD28-, Effector memory (EMRA null/dim), and the CD16+/CD56 + CD8+ T cells of women with low-grade cervical lesions are altered at a systemic level. Methods: We enrolled in this study women controls and women with Human papilloma virus infection (HPV-I) without associated cellular neoplastic changes and with Cervical Intraepithelial Neoplastic-I (CIN-I). Flow cytometry (FC) was performed for measurement of CD28-, memory subset, and NK-like CD8 + T cells, and IL-17, IFN-gamma, Tumor necrosis factor (TNF)-alpha, Interleukin (IL)-10, IL-6, IL-4, and IL-2. Finally, we genotyped the HPV. Results: The CIN-I group increased the CD8 + CD28− and CD16+/56+ T cell percentage compared with that of HPV-I and controls (p <0.01), and CD8 + CCR7-CD45RA null/dim (EMRA null/dim) T cells were also increased in the CIN-I group compared with the controls (p <0.01). These two study groups were HPV-genotyped; 49% were HPV18+, and we did not observe differences in cytokine levels among all groups. Conclusions: Increased levels of CD28-, EMRA null/dim , and CD16+/CD56 + CD8+ T cells of peripheral blood in women with CIN-I may be associated with persistent HPV infection and could exert an influence on progression to cervical cancer.
Infiltrating CD4 and CD8 lymphocytes in HPV infected uterine cervical milieu
Cancer Management and Research
Purpose: Tumor infiltrating lymphocytes (TILs) have been extensively described in antitumor immunity, but their functional alterations in the immunoediting processes during neoplastic progression in the uterine cervix are still not clear. Our aim was to gain insight into cervical tissue T cell populations, determine if there are any differences in the localization and quantity distribution of T lymphocytes, and to evaluate their role in disease regression or progression in the cervical neoplastic milieu. Patients and methods: Serial section analysis of immunohistochemically stained CD4 and CD8 lymphocytes was performed on a total number of 72 samples, categorized into four cohorts: 23 HPV non-infected (HPV-) normal cervix, 20 HPV infected (HPV+) normal cervix, 17 HPV+ low grade cervical intraepithelial neoplasia (CIN), and 12 HPV+ high grade CIN. Results: Low infiltrating lymphocytes (ILs) in normal cervix and high ILs in CIN were observed, while the trend of ILs increased with increasing grade of CIN, which was statistically significant (P<0.0001). Quantitative and localization analysis between the subsets of T cells showed that, in the epithelial layer, infiltrating CD8+ lymphocytes (CD8+ ILs) were significantly higher than CD4+ ILs in HPV+ normal cervix, while the trend decreased with increasing grade of CIN (P=0.011). Whereas, in the stromal layer, CD4+ ILs were predominant in all study groups and no statistical difference was found between these groups. However, tumor infiltrating CD8+ lymphocytes (CD8+ TILs) were noted to be significantly higher than CD4+ TILs in severe dysplastic cases. Conclusion: T cell infiltrates were predominant as the grade of the lesion progressed into more advanced lesions, which likely represent the lesions that have persisted over time. The variation in the infiltration rate and the location of CD4+ ILs and CD8 ILs may suggest the efficacious role of CD8 T cells in eliminating HPV infected cervical epithelial cells and also provides insight into the complex role of TILs in facilitating and mediating sustained antitumor responses, hence preventing tumor outgrowth.
HPV Infection: Immunological Aspects and Their Utility in Future Therapy
Infectious Diseases in Obstetrics and Gynecology, 2013
High prevalence and mortality rates of cervical cancer create an imperative need to clarify the uniqueness of HPV (Human Papillomavirus) infection, which serves as the key causative factor in cervical malignancies. Understanding the immunological details and the microenvironment of the infection can be a useful tool for the development of novel therapeutic interventions. Chronic infection and progression to carcinogenesis are sustained by immortalization potential of HPV, evasion techniques, and alterations in the microenvironment of the lesion. Inside the lesion, Toll-like receptors expression becomes irregular; Langerhans cells fail to present the antigens efficiently, tumor-associated macrophages aggregate resulting in an unsuccessful immune response by the host. HPV products also downregulate the expression of microenvironment components which are necessary for natural-killer cells response and antigen presentation to cytotoxic cells. Additionally HPV promotes T-helper cell 2 (T...
Clinical Immunology, 2010
Background: The NKG2D receptor confers important activating signals to NK cells via ligands expressed during cellular stress and viral infection. This receptor has generated great interest because not only is it expressed on NK cells, but it is also seen in virtually all CD8 + cytotoxic T cells and is classically considered absent in CD4 + T cells. However, recent studies have identified a distinctive population of CD4 + T cells that do express NKG2D, which could represent a particular cytotoxic effector population involved in viral infections and chronic diseases. On the other hand, increased incidence of human papillomavirus-associated lesions in CD4 + T cell-immunocompromised individuals suggests that CD4 + T cells play a key role in controlling the viral infection. Therefore, this study was focused on identifying the frequency of NKG2D-expressing CD4 + T cells in patients with cervical intraepithelial neoplasia (CIN) 1. Additionally, factors influencing CD4 + NKG2D + T cell expansion were also measured.
Immunobiology of HPV Infection
Archives of medical research, 2009
Although the high-risk human papillomavirus (HPV) is necessary to cause cervical cancer (CC) and its infectious origin is well recognized, neither the systemic nor the local immune responses to this virus has been well studied or understood. Because the many facets of HPV are excellently described here by others, we will focus on the immune responses of the female genital tract, especially in situ, or in natura, as Casanova argues when studying diseases (1). A general overview is provided where different elements of the innate and adaptive immunity are discussed. We highlight the very successful strategy used by HPV with a protracted and seemingly silent infection, making this virus extremely well adapted to infect humans. The counterpart of this peculiar immunological situation is that whatever immune responses (innate or adaptive, local or systemic) are induced in those chronically infected women, these responses are inefficient to cope with and especially to eradicate the virus, thus resulting in viral persistence. A further follow-up of this line of thought is that among other well-known co-factors some still uncovered complex immune alterations may underlie the enigmatic susceptibility of the minority of women permissive to the chronic HPV infection, i.e., of those who slowly progress from infection to CIN 1e2e3 and then to invasive cervical carcinoma.
Gynecologic Oncology, 2005
Objectives. The specific CTL response against human papillomavirus (HPV) antigens in women with cervical cancer has been poorly studied. Immunological monitoring of this response is central for understanding the principles that underlie successful immunotherapeutic strategies. The aim of the study was to investigate the HPV16 E6/E7-specific CTL immune response in a group of untreated HPV16-positive cervical cancer patients.