Interleukin 2 production in vitro by peripheral lymphocytes in response to human papillomavirus-derived peptides: correlation with cervical pathology.
Human papillomavirus (HPV) is believed to be the major cause of cervical cancer. To investigate whether a cellular immune response, especially a T helper type 1 response, is related to the natural defense against HPV-related cervical lesions, the interleukin 2 response of peripheral blood lymphocytes in vitro to overlapping peptides from HPV-16 E6 and E7 oncoproteins was compared with the degree of cervical cytological abnormality among 140 women in a cross-sectional study. We compared 66 women diagnosed with low-grade squamous intraepithelial lesions (LSIL), 21 with high-grade squamous intraepithelial lesions (HSIL), and 28 with invasive cervical cancer with 25 women who were cytologically normal but previously HPV-16 DNA positive. The fraction showing strong interleukin 2 production against HPV-16 peptides was greatest among cytologically normal women (35%) and declined with increasing disease severity [LSIL] (20%), HSIL, (17%), and cancer patients (7%); X2 test P for the trend = 0.02], whereas the responses against a recall influenza antigen were not significantly different among groups. Our finding suggests that a T helper lymphocyte type 1 response to HPV antigens is associated with disease status. This result may reflect a targeted effect of the disease on immune function or a protective effect of the immune response against disease progression.
Tsukui
T
T
Molecular Immunogenetics and Vaccine Research Section, National Cancer Institute, Bethesda, Maryland 20892, USA.
Hildesheim
A
A
Schiffman
M H
MH
Lucci
J
J
Contois
D
D
Lawler
P
P
Rush
B B
BB
Lorincz
A T
AT
Corrigan
A
A
Burk
R D
RD
Qu
W
W
Marshall
M A
MA
Mann
D
D
Carrington
M
M
Clerici
M
M
Shearer
G M
GM
Carbone
D P
DP
Scott
D R
DR
Houghten
R A
RA
Berzofsky
J A
JA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000097:blood; D008213:Lymphocyte Activation; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D009856:Oncogene Proteins, Viral / Q000494:pharmacology*; D027383:Papillomaviridae / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000097:blood / Q000276:immunology; D012097:Repressor Proteins; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology*; D014412:Tumor Virus Infections / Q000097:blood / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000473:pathology* / Q000821:virology*
D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D007376:Interleukin-2; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16