Depressed type 1 cytokine synthesis by superantigen-activated CD4+ T cells of women with human papillomavirus-related high-grade squamous intraepithelial lesions.
Carcinoma of the cervix is causally related to infection with the human papillomavirus (HPV), and T cells play a pivotal role in the immune response of the host to rid itself of HPV infection. Therefore, we assessed the T-cell function of women with HPV-related cervical neoplasia against a superantigen, Staphylococcus enterotoxin B (SEB). Each woman provided a cervical brush specimen for HPV DNA testing and Papanicolaou (Pap) smears for the staging of cervical lesions. They also provided a blood specimen for determination of the ability of CD4(+) T and CD8(+) T cells to synthesize Th1 (interleukin-2 [IL-2], gamma interferon [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]) and Th2 (IL-10) cytokines in response to activation with SEB. Compared with control subjects with self-attested negative Pap smears, women with high-grade squamous intraepithelial lesions (HSIL) had significantly lower percentages of activated CD4(+) T cells that produced IL-2 (P = 0.045), IFN-gamma (P = 0.040), and TNF-alpha (P = 0.015) and a significantly lower percentage of activated CD8(+) T cells that produced IL-2 (P < 0.01). These data indicate that women with HPV-related cervical HSIL show a decrease in Th1 cytokine production by activated CD4(+) T cells and suggested that compromised T-helper functions may negatively impact the function of cytotoxic CD8(+) T cells.
Lee
Bang-Ning
BN
Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. blee@mdanderson.org
Follen
Michele
M
Shen
De-Yu
DY
Malpica
Anais
A
Adler-Storthz
Karen
K
Shearer
William T
WT
Reuben
James M
JM
D000942:Antigens, Bacterial / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002584:Cervix Uteri / Q000276:immunology / Q000473:pathology* / Q000821:virology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D004768:Enterotoxins / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D009367:Neoplasm Staging; D030361:Papillomavirus Infections / Q000276:immunology* / Q000473:pathology; D011230:Precancerous Conditions / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018089:Superantigens / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000473:pathology / Q000821:virology
D000942:Antigens, Bacterial; D016207:Cytokines; D004768:Enterotoxins; D007376:Interleukin-2; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma