Ortiz-Sánchez E, Chávez-Olmos P, Piña-Sánchez P, Salcedo M, Garrido E
Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del IPN, México DF.
Int J Gynecol Cancer. 2007 May-Jun;17(3):571-80. doi: 10.1111/j.1525-1438.2007.00904.x. Epub 2007 Mar 26.
Keratinocytes have been traditionally considered as nonprofessional antigen presenting cells, since multipassaged cells from skin biopsies of healthy individuals do not constitutively express major histocompatibility complex (MHC) class II or costimulatory molecules, but can be induced to do so after exposure to interferon-gamma. In normal and human papillomavirus (HPV)-infected cervical epithelium, keratinocytes are affected by a variety of soluble mediators that could modulate the expression of molecules including costimulatory proteins; however, the presence of these molecules within the cervix has been poorly studied. Therefore, our aim was to further explore the presence of costimulatory molecules on normal cervical epithelium and HPV-16 positive low squamous intraepithelial lesions (LSIL). We found in situ CD86 (but not CD80) displayed on the surface of normal keratinocytes from the spinous layer of human cervical epithelium. The presence of the protein and its messenger RNA level (evaluated by in situ hybridization) was diminished in HPV-16 positive LSILs. Although downregulation of costimulatory molecules is frequently related to cytokines expression, we did not observe differences in the presence of interleukin-10, the main cytokine that inhibits CD86 expression. Expression of CD86 on keratinocytes from normal cervical epithelium could indicate the potentiality of these cells to activate cytotoxic T cells, while the shut-off of this molecule in HPV-16 positive lesions could be a mechanism for evading host immune surveillance, resulting in the persistent HPV infection and probable progression of cervical lesions.
传统上,角质形成细胞被认为是非专职抗原呈递细胞,因为从健康个体皮肤活检中多次传代培养的细胞不会组成性表达主要组织相容性复合体(MHC)II类分子或共刺激分子,但在接触γ干扰素后可被诱导表达。在正常和人乳头瘤病毒(HPV)感染的宫颈上皮中,角质形成细胞会受到多种可溶性介质的影响,这些介质可调节包括共刺激蛋白在内的分子表达;然而,这些分子在宫颈内的存在情况研究较少。因此,我们的目的是进一步探究正常宫颈上皮和HPV-16阳性低级别鳞状上皮内病变(LSIL)中共刺激分子的存在情况。我们发现,人宫颈上皮棘层正常角质形成细胞表面原位显示有CD86(而非CD80)。在HPV-16阳性LSIL中,该蛋白及其信使核糖核酸水平(通过原位杂交评估)降低。虽然共刺激分子的下调通常与细胞因子表达有关,但我们并未观察到抑制CD86表达的主要细胞因子白细胞介素-10的存在有差异。正常宫颈上皮角质形成细胞上CD86的表达可能表明这些细胞具有激活细胞毒性T细胞的潜力,而在HPV-16阳性病变中该分子的关闭可能是逃避宿主免疫监视的一种机制,导致HPV持续感染以及宫颈病变可能进展。