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Accumulation of invariant NKT cells with increased IFN-γ production in persistent high-risk HPV-infected high-grade cervical intraepithelial neoplasia.

Hu T, Yang P, Zhu H, Chen X, Xie X, Yang M, Liu S, Wang H - Diagn Pathol (2015)

Bottom Line: A significant increase in iNKT cells was observed in HPV-positive cervical tissues (p < 0.05), especially in CINII-III (p < 0.01).IFN-γ expression was also increased in HPV-positive cervical tissues (p < 0.05).Preventing the accumulation or functioning of iNKT cells in cervical tissues may be a viable method to prevent the development of CIN.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. huting4123@163.com.

ABSTRACT

Background: Persistent high-risk human papillomavirus (HR-HPV) infection has been implicated in the development of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer. Invariant natural killer T (iNKT) cells produce large amounts of cytokines to regulate immune responses. However, the role of iNKT cells in human persistent HPV-infected cervical tissues is unknown.

Methods: In our study, 201 patients with diagnoses ranging from normal ectocervical tissue to CINIII from June 2010 to May 2012 were enrolled. HPV DNA and HPV types were detected using the hybrid capture-2 HPV DNA test. Flow cytometry was used to investigate iNKT and CD3+ T cell infiltration into cervical tissues. Real-time quantitative reverse transcription-polymerase chain reaction was used to study IFN-γ expression and immunohistochemistry was used to determine CD3+ T cell distribution.

Results: A significant increase in iNKT cells was observed in HPV-positive cervical tissues (p < 0.05), especially in CINII-III (p < 0.01). IFN-γ expression was also increased in HPV-positive cervical tissues (p < 0.05). CD3+ T cells were detected among both epithelium and stromal layers in cervical tissues, and the percentage of CD3+ T cells in HPV-positive cervical tissues was similar to that in HPV-negative cervical tissues (p > 0.05).

Conclusions: The iNKT cell aggregation in cervical tissues during the progression from HPV infection to CIN indicates that iNKT cells might play an important role in suppressing immunity. IFN-γ expression could also be related to the HPV infection status. Preventing the accumulation or functioning of iNKT cells in cervical tissues may be a viable method to prevent the development of CIN.

Virtual slides: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2521874671514142.

No MeSH data available.


Related in: MedlinePlus

The distribution of CD3+ T cells in HPV-positive cervical tissues is similar to that in HPV-negative cervical tissues, but significantly increased in CINIII cervical tissues. A, a1 and a2, IHC of CD3+ T cells in HPV-positive cervical tissues detected by CD3 staining (IHC 10× and 100×); b1 and b2, IHC of CD3+ T cells in HPV-negative cervical tissues detected by CD3 staining (IHC × 10 and × 100). B, The bar graph shows CD3+ T cells as percentages of cervical tissues isolated from the HPV-positive and HPV-negative groups (p = 0.528). C, a1 and a2, IHC of CD3+ T cells in CINIII cervical tissues detected by CD3 staining (IHC 10× and 100×); b1 and b2, IHC of CD3+ T cells in all other < CINIII cervical tissues detected by CD3 staining (IHC 10× and 100×). D, The bar graph shows CD3+ T cells as percentages of cervical tissues isolated from CINIII and all other < CINIII cervical tissues (*p = 0.001).
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Fig2: The distribution of CD3+ T cells in HPV-positive cervical tissues is similar to that in HPV-negative cervical tissues, but significantly increased in CINIII cervical tissues. A, a1 and a2, IHC of CD3+ T cells in HPV-positive cervical tissues detected by CD3 staining (IHC 10× and 100×); b1 and b2, IHC of CD3+ T cells in HPV-negative cervical tissues detected by CD3 staining (IHC × 10 and × 100). B, The bar graph shows CD3+ T cells as percentages of cervical tissues isolated from the HPV-positive and HPV-negative groups (p = 0.528). C, a1 and a2, IHC of CD3+ T cells in CINIII cervical tissues detected by CD3 staining (IHC 10× and 100×); b1 and b2, IHC of CD3+ T cells in all other < CINIII cervical tissues detected by CD3 staining (IHC 10× and 100×). D, The bar graph shows CD3+ T cells as percentages of cervical tissues isolated from CINIII and all other < CINIII cervical tissues (*p = 0.001).

Mentions: To confirm the distribution of CD3+ T cells in cervical tissues, we immunostained HPV-positive (n = 44) and HPV-negative cervical tissue (n = 23) for CD3. Immunoreactivity with an anti-CD3 Ab was noted in both epithelium and stromal layers from formalin-fixed, paraffin-embedded cervical tissue sections. There were no significant differences in CD3 expression between HPV-positive and HPV-negative tissues (mean, 0.900% vs. 0.868%, p = 0.528) (Figure 2A, B). Similar to the flow cytometry results, CD3 expression was significantly increased in CINIII samples (n = 13) compared to all of the other samples (n = 54) (mean, 1.108% vs. 0.820%, p = 0.001) (Figure 2C, D).Figure 2


Accumulation of invariant NKT cells with increased IFN-γ production in persistent high-risk HPV-infected high-grade cervical intraepithelial neoplasia.

Hu T, Yang P, Zhu H, Chen X, Xie X, Yang M, Liu S, Wang H - Diagn Pathol (2015)

The distribution of CD3+ T cells in HPV-positive cervical tissues is similar to that in HPV-negative cervical tissues, but significantly increased in CINIII cervical tissues. A, a1 and a2, IHC of CD3+ T cells in HPV-positive cervical tissues detected by CD3 staining (IHC 10× and 100×); b1 and b2, IHC of CD3+ T cells in HPV-negative cervical tissues detected by CD3 staining (IHC × 10 and × 100). B, The bar graph shows CD3+ T cells as percentages of cervical tissues isolated from the HPV-positive and HPV-negative groups (p = 0.528). C, a1 and a2, IHC of CD3+ T cells in CINIII cervical tissues detected by CD3 staining (IHC 10× and 100×); b1 and b2, IHC of CD3+ T cells in all other < CINIII cervical tissues detected by CD3 staining (IHC 10× and 100×). D, The bar graph shows CD3+ T cells as percentages of cervical tissues isolated from CINIII and all other < CINIII cervical tissues (*p = 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4416328&req=5

Fig2: The distribution of CD3+ T cells in HPV-positive cervical tissues is similar to that in HPV-negative cervical tissues, but significantly increased in CINIII cervical tissues. A, a1 and a2, IHC of CD3+ T cells in HPV-positive cervical tissues detected by CD3 staining (IHC 10× and 100×); b1 and b2, IHC of CD3+ T cells in HPV-negative cervical tissues detected by CD3 staining (IHC × 10 and × 100). B, The bar graph shows CD3+ T cells as percentages of cervical tissues isolated from the HPV-positive and HPV-negative groups (p = 0.528). C, a1 and a2, IHC of CD3+ T cells in CINIII cervical tissues detected by CD3 staining (IHC 10× and 100×); b1 and b2, IHC of CD3+ T cells in all other < CINIII cervical tissues detected by CD3 staining (IHC 10× and 100×). D, The bar graph shows CD3+ T cells as percentages of cervical tissues isolated from CINIII and all other < CINIII cervical tissues (*p = 0.001).
Mentions: To confirm the distribution of CD3+ T cells in cervical tissues, we immunostained HPV-positive (n = 44) and HPV-negative cervical tissue (n = 23) for CD3. Immunoreactivity with an anti-CD3 Ab was noted in both epithelium and stromal layers from formalin-fixed, paraffin-embedded cervical tissue sections. There were no significant differences in CD3 expression between HPV-positive and HPV-negative tissues (mean, 0.900% vs. 0.868%, p = 0.528) (Figure 2A, B). Similar to the flow cytometry results, CD3 expression was significantly increased in CINIII samples (n = 13) compared to all of the other samples (n = 54) (mean, 1.108% vs. 0.820%, p = 0.001) (Figure 2C, D).Figure 2

Bottom Line: A significant increase in iNKT cells was observed in HPV-positive cervical tissues (p < 0.05), especially in CINII-III (p < 0.01).IFN-γ expression was also increased in HPV-positive cervical tissues (p < 0.05).Preventing the accumulation or functioning of iNKT cells in cervical tissues may be a viable method to prevent the development of CIN.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. huting4123@163.com.

ABSTRACT

Background: Persistent high-risk human papillomavirus (HR-HPV) infection has been implicated in the development of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer. Invariant natural killer T (iNKT) cells produce large amounts of cytokines to regulate immune responses. However, the role of iNKT cells in human persistent HPV-infected cervical tissues is unknown.

Methods: In our study, 201 patients with diagnoses ranging from normal ectocervical tissue to CINIII from June 2010 to May 2012 were enrolled. HPV DNA and HPV types were detected using the hybrid capture-2 HPV DNA test. Flow cytometry was used to investigate iNKT and CD3+ T cell infiltration into cervical tissues. Real-time quantitative reverse transcription-polymerase chain reaction was used to study IFN-γ expression and immunohistochemistry was used to determine CD3+ T cell distribution.

Results: A significant increase in iNKT cells was observed in HPV-positive cervical tissues (p < 0.05), especially in CINII-III (p < 0.01). IFN-γ expression was also increased in HPV-positive cervical tissues (p < 0.05). CD3+ T cells were detected among both epithelium and stromal layers in cervical tissues, and the percentage of CD3+ T cells in HPV-positive cervical tissues was similar to that in HPV-negative cervical tissues (p > 0.05).

Conclusions: The iNKT cell aggregation in cervical tissues during the progression from HPV infection to CIN indicates that iNKT cells might play an important role in suppressing immunity. IFN-γ expression could also be related to the HPV infection status. Preventing the accumulation or functioning of iNKT cells in cervical tissues may be a viable method to prevent the development of CIN.

Virtual slides: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2521874671514142.

No MeSH data available.


Related in: MedlinePlus