- 作者: Mariel Garcia-Chagollan, Luis Felipe Jave-Suarez, Jesse Haramati, Miriam Ruth Bueno-Topete, Adriana Aguilar-Lemarroy, Ciro Estrada-Chavez, Blanca Estela Bastidas-Ramirez, Ana Laura Pereira-Suarez , Susana del Toro-Arreola
- 作者服務機構: Departamento de Fisiologia, Laboratorio de Inmunologia, CUCS, Universidad de Guadalajara, Sierra Mojada, Guadalajara, Jalisco, Mexico
- 中文摘要: --
- 英文摘要:
Background:
NKG2D, an activating immunoreceptor, is primarily restricted to NK cells and CD8 + T cells. The existence of an atypical cytotoxic CD4 + NKG2D + T cell population has also been found in patients with autoimmune dysfunctions. Nonetheless, contradictory evidence has categorized this population with a regulatory rather than cytotoxic role in other situations. These confounding data have led to the proposal that two distinct CD4 + NKG2D + T cell subsets might exist. The immune response elicited in cervical cancer has been characterized by apparent contradictions concerning the role that T cells, in particular T-helper cells, might be playing in the control of the tumor growth. Interestingly, we recently reported a substantial increase in the frequency of CD4 + NKG2D + T cells in patients with cervical intraepithelial neoplasia grade-1. However, whether this particular population is also found in patients with more advanced cervical lesions or whether they express a distinctive phenotype remains still to be clarified. In this urgent study, we focused our attention on the immunophenotypic characterization of CD4 + NKG2D + T cells in patients with well-established cervical carcinoma and revealed the existence of at least two separate CD4 + NKG2D + T cell subsets defined by the co-expression or absence of CD28.
Results:
Patients with diagnosis of invasive cervical carcinoma were enrolled in the study. A group of healthy individuals was also included. Multicolor flow cytometry was used for exploration of TCR alpha/beta, CD28, CD158b, CD45RO, HLA-DR, CD161, and CD107a. A Luminex-based cytokine kit was used to quantify the levels of pro- and anti-inflammatory cytokines. We found an increased percentage of CD4 + NKG2D + T cells in patients with cervical cancer when compared with controls. Accordingly with an increase of CD4 + NKG2D + T cells, we found decreased CD28 expression. The activating or degranulation markers HLA-DR, CD161, and CD107a were heterogeneously expressed. The levels of IL-1beta, IL-2, TNF-alpha, and IL-10 were negatively correlated with the percentages of CD4 + NKG2D + T cells in patients with cervical carcinoma.
Conclusions:
Taken together, our results reveal the existence of two separate CD4 + NKG2D + T cell subsets defined by the co-expression or absence of CD28, the latter more likely to be present in patients with cervical cancer. - 中文關鍵字: --
- 英文關鍵字: NKG2D; CD4+NKG2D+ T cells; Cervical carcinoma