Expansion of the CD8 + CD45RA + CD27 - CD28 - T-Cell Subset in Patients with HPV-Associated Cervical Cancer and its Precursors

Summary

Objective

More than 90 % of cervical cancers and precursors are caused by infection with high-risk human papillomavirus (HPV). Cellular immune responses associated with HPV may be detectable in peripheral blood. The purpose of the present study was to assess the immune status in patients with HPV-infection and to identify T cell subsets which may serve as a surrogate marker for immune activation induced bei HPV.

Methods

Subsets of peripheral blood lymphocytes in women (n = 30) without signs of HPV-infection were compared with those of patients with histologically verified HPV-associated cervical intraepithelial neoplasia (CIN) (n = 22) or invasive cervical carcinomas (n = 16) using four-color flow cytometric analysis.

Results

One of the major changes in the T cell repertoire was a significant expansion of T cells characterized by the CD8+ CD45RA+ CD27- CD28- immune phenotype in patients with HPV associated CIN and cancer compared with the control group (p < 0.01 and 0.0001, respectively). This immune phenotype also differed significantly (p < 0.04) between patients with CIN and CC.

Conclusion

The significant T cell response in patients with HPV associated CIN and cancer suggests a proliferative expansion of HPV-antigen-experienced cytotoxic T cells. Further studies are necessary to determine the viral specificity and the validity of lymphocyte subset analysis for monitoring immune function in patients with HPV-associated neoplasia.

Zusammenfassung

Fragestellung

Die Beurteilung des Immunstatus bzw. eines Krankheitsprogresses bei Patienten mit chronischen Virusinfektionen ist oftmals durch die Untersuchung des peripheren Blutes möglich. Mehr als 90 % aller Dysplasien und Neoplasien der Zervix werden durch eine Infektion mit den humanen Papillomaviren vom High-risk-Typ verursacht, welche möglicherweise mit einer spezifischen zellulären Immunantwort verbunden ist. Das Ziel dieser Untersuchung war die Beurteilung des Immunstatus bei HPV-positiven Patientinnen und die Identifizierung eines bestimmten T-Zell-Repertoires, das möglicherweise als Surrogatmarker für eine HPV-spezifische zelluläre Immunaktivierung dienen könnte.

Material und Methodik

Die Subpopulation der peripheren Blutlymphozyten (PBL) von 30 Patientinnen (n = 30) ohne Zeichen einer HPV-Infektion wurden mit denen von Patientinnen mit histologisch gesicherter zervikaler intraepithelialer Neoplasie (CIN) (n = 22) und invasivem Zervixkarzinom (CC) (n = 16) mittels 4-Farben-Durchflusszytometrie verglichen.

Ergebnisse

Als eine signifikante Veränderung im T-Zell-Repertoire fand sich ein Anstieg der CD8 + CD45RA + CD27 - CD28 - T-Zell-Subpopulation bei Patientinnen mit HPV-assoziierter CIN und CC im Vergleich zur Kontrollgruppe (p < 0,01 resp. 0,0001). Selbst zwischen Patienten mit CIN und CC ließ sich ein signifikanter Unterschied in dieser T-Zell-Subpopulation objektivieren (p < 0,04).

Schlussfolgerung

Unsere Untersuchungen zeigen eine signifikante T-Zell-Antwort bei Patientinnen mit HPV-assoziierter Dysplasie bzw. Neoplasie der Cervix uteri in Form einer Proliferation von (HPV) antigen-erfahrenen zytotoxischen T-Lymphozyten-Analysen für das klinische Immunmonitoring bei Patienten mit HPV-assoziierter zervikaler Neoplasie zu belegen.

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