Substantial increase in the frequency of circulating CD4+NKG2D+ T cells in patients with cervical intraepithelial neoplasia grade 1.
BACKGROUND
The NKG2D receptor confers important activating signals to NK cells via ligands expressed during cellular stress and viral infection. This receptor has generated great interest because not only is it expressed on NK cells, but it is also seen in virtually all CD8+ cytotoxic T cells and is classically considered absent in CD4+ T cells. However, recent studies have identified a distinctive population of CD4+ T cells that do express NKG2D, which could represent a particular cytotoxic effector population involved in viral infections and chronic diseases. On the other hand, increased incidence of human papillomavirus-associated lesions in CD4+ T cell-immunocompromised individuals suggests that CD4+ T cells play a key role in controlling the viral infection. Therefore, this study was focused on identifying the frequency of NKG2D-expressing CD4+ T cells in patients with cervical intraepithelial neoplasia (CIN) 1. Additionally, factors influencing CD4+NKG2D+ T cell expansion were also measured.


RESULTS
Close to 50% of patients with CIN 1 contained at least one of the 37 HPV types detected by our genotyping system. A tendency for increased CD4+ T cells and CD8+ T cells and decreased NK cells was found in CIN 1 patients. The percentage of circulating CD4+ T cells co-expressing the NKG2D receptor significantly increased in women with CIN 1 versus control group. Interestingly, the increase of CD4+NKG2D+ T cells was seen in patients with CIN 1, despite the overall levels of CD4+ T cells did not significantly increase. We also found a significant increase of soluble MICB in CIN 1 patients; however, no correlation with the presence of CD4+NKG2D+ T cells was seen. While TGF-beta was significantly decreased in the group of CIN 1 patients, both TNF-alpha and IL-15 showed a tendency to increase in this group.


CONCLUSIONS
Taken together, our results suggest that the significant increase within the CD4+NKG2D+ T cell population in CIN 1 patients might be the result of a chronic exposure to viral and/or pro-inflammatory factors, and concomitantly might also influence the clearance of CIN 1-type lesion.
Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada # 950, Colonia Independencia, Guadalajara, Jalisco CP 44340, México.
Mariel
M
Garcia-Chagollan
Luis F
LF
Jave-Suarez
Jesse
J
Haramati
Pedro E
PE
Sanchez-Hernandez
Adriana
A
Aguilar-Lemarroy
Miriam R
MR
Bueno-Topete
Ana L
AL
Pereira-Suarez
Mary
M
Fafutis-Morris
Angel
A
Cid-Arregui
Susana
S
del Toro-Arreola
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000378:metabolism*; D060787:Neoplasm Grading; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D027383:Papillomaviridae / Q000235:genetics / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000473:pathology / Q000821:virology
D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; D055655:NK Cell Lectin-Like Receptor Subfamily K; D014409:Tumor Necrosis Factor-alpha