Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
Cytokine production in response to human papillomavirus (HPV) 16 E6 and E7 peptides in patients (pts) with low-grade squamous intra-epithelial lesions (SIL) and correlation with follow-up cervical cytology (Meeting abstract).
Proc Annu Meet Am Soc Clin Oncol; 16:A1293 1997. Unique Identifier : AIDSLINE ICDB/98643293 Timmins P; Wang Y; Fan Z; Ho G; Fields A; Goldberg G; Runowicz C; Qu W; Kadish A; Albert Einstein College of Medicine, Bronx, NY
Abstract:
Our laboratory has previously demonstrated that the presence of T cell lymphoproliferative (LP) responses to peptides from the E6 and E7 oncogenic proteins of HPV 16 correlated with resolution of HPV Infection, regression of squamous intraepithelial lesions (SIL), and with resolution of SIL by cervical cytology. These responses have not been separated into T helper cell type 1 (TH1), associated with cytotoxic T cell response, versus T helper type 2 (TH2), associated with antibody response. Our hypotheses are that pts with low grade SIL are more likely to make a TH1 response and that those with this response will be more likely to clear their SIL spontaneously than pts who make a TH2 response. We correlated LP responses to E6 and E7 peptides with presence of interferon-gamma (IFN-g), consistent with TH1 response, and/or Interleukin-4 (IL-4), consistent with a TH2 response, by sandwich enzyme linked immunosorbent assay (ELISA) from culture supernatants. 16 untreated pts with biopsy proven low grade SIL and HPV infection detected by PCR who had LP responses (LP+) to E6 and E7 peptides of peripheral blood mononuclear cells (PBMC) were assessed. Three pools of peptides were tested: N-terminal and C-terminal E6, and an E7 pool, using peptides that yield positive LP responses. An LP positive (LP+) response was defined as stimulation index of 4.0 or more. Supernatants from these cultures that were LP+ were assessed for presence of IFN-g using a commercial ELISA kit. 10 pts (63%) were LP+ and IFN-g+. Of 6 pts who were IFN-g-, 4 were IL4+ and 2 were not yet tested. In 13 pts, cytokine production was correlated with follow-up Pap smear results. 9/13 (69%) were IFN-g+ and 4/13 (31%) IFN-g-. In 7/9 pts (78%) who were IFN-g+, follow-up Pap smears were normal, negative for SIL. Whereas, 2/4 (50%) pts who were IFN-g- had follow-up Pap smears negative for SIL (p = .10). These 2 pts did not have IL-4 analyzed. 2 of the IFN-g- but IL-4+ pts were the only pts with persistent high grade SIL on follow-up Pap smear. 2 of the IFN-g-, IL4+ pts did not have follow-up Pap smears yet. The data suggest that: (1) pts with low grade SIL make TH1 responses; (2) TH1 cytotoxic responses may be protective and may lead to spontaneous regression of SIL; (3) TH2 responses may be associated with persistent disease and perhaps enhanced risk of progression.
Keywords: Cervical Intraepithelial Neoplasia/*METABOLISM/PATHOLOGY Cytokines/*BIOSYNTHESIS Enzyme-Linked Immunosorbent Assay Human Oncogene Proteins, Viral/*METABOLISM Papillomavirus, Human/METABOLISM Polymerase Chain Reaction Th1 Cells/IMMUNOLOGY/METABOLISM Th2 Cells/IMMUNOLOGY/METABOLISM Vaginal Smears ABSTRACT 980228
M9820749
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Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
