Subpopulations of Langerhans' cells in cervical neoplasia

Abstract

Multiple markers were used to count Langerhans' cells in the cervix. In the normal cervix, thymocyte antigen (T6) and adenosine triphosphatase ( ATPase) demonstrated the largest population of Langerhans' cells. MHC Class 11 positive cells were equivalent to 60%, and SlOO positive cells were equivalent to 35% of T6 or ATPase positive cells, Whereas Langerhans' cells demonstrated by T6, ATPase, and MHC Class I1 antigen were evenly distributed throughout the epithelium, the SlOO positive cells were seen predominantly near lymphocytic aggregates and capillaries. In human papillomavirus infection and cervical intraepithelial neoplasia the numbers of T6, ATPase, or MHC Class I1 positive Langerhans' cells were reduced by 60% but the SlOO positive cells were almost completely depleted. These findings suggested that there were different subpopulations of Langerhans' cells in the cervical epithelium. The depletion of Langerhans' cells, particularly the selective depletion of the SlOO positive subpopulation, might cause a localized immunodeficiency that impairs immune surveillance and the cell-mediated immune response to human papillomavirus infection and cervical intraepithelial neoplasia.Human papillomavirus (HPV), types 16 and 18in particular, appears to be an important aetiological factor in the development of cervical neoplasia (Gissman ef al. 1983;McCance et al. 1985; Kreider et al. 1985). Viral pathogenesis is the outcome of interaction between the virulence of the virus and the host immune

Co-fatores do HPV na oncogênese cervical

“…Alterações verificadas no sistema imune periférico de pacientes fumantes incluem a elevação do número de células sangüíneas, o aumento do número de linfócitos T citotóxicos/supressores, a diminuição do número de linfócitos T indutores/auxiliares, discreta supressão da atividade de linfócitos T, significativo decréscimo da atividade de linfócitos natural killer, e baixos níveis sangüíneos de imunoglobulinas, exceto pela IgE, a qual é elevada 27 . Uma diminuição do número de células de Langerhans na cervix de mulheres fumantes tem sido observada por muitos autores 43,50 . Este dado experimental é apoiado por estudos clínicos que revelam a associação do hábito de fumar e história de condições immunosupressivas em pacientes jovens com doença invasiva cervical 43 .…”

Advances in Peptide-based Human Papillomavirus Therapeutic Vaccines

“…2) The E6 oncoprotein inhibits the interactions between epithelial cells and DCs [58], possibly accounting for the depletion of DCs observed in the HPV-infected cervical epithelium [59]. An E6 oncoprotein-mediated reduction in expressed interleukin-8 (IL-18) CD8 + was also observed [60].…”

“…The lipid core peptide (LCP), a vaccine delivery system incorporating lipoamino acids, was used to produce vaccine candidates against HPV-16 [104]. Moyle et al demonstrated that an LCP system that incorporated the long sequence E7 [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] (known as 8Q) with CTL, T helper cell, and B cell epitopes was self-adjuvanting and reduced tumor size. This epitope was unable to prevent TC-1 tumors when delivered alone [104].…”

“…The self-adjuvanting properties of LCP are predominantly derived from its propensity to target vaccines to DCs and induce DC maturation [22,112]. In another mouse study, a lipopeptide vaccine incorporated the E6 [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57] and E7 [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] epitopes conjugated to a dipalmitoyl-lysine-glycineglycine (Pam 2 KGG) moiety. It was shown that although both epitopes were individually able to elicit specific CTL responses in mice, the lipid-tailed (Pam 2 KGG) diepitopic construct was more efficient than the monomeric forms [113].…”

“…Another animal study, which used a long peptide (E7 [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] ) and the DC-activating adjuvant ODN-CpG, has identified that vaccination with a longer peptide containing CTL and Th cell epitopes, and ODN-CpG represents a promising strategy against MHC-I deficient tumors. This study also investigated the efficacy of cellular vaccines based on ex vivo cultured DCs pulsed with either minimal CTL (E7 [49][50][51][52][53][54][55][56][57] ) epitope or longer CTL (E7 [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] ) epitopes, and then matured with ODNCpG. The use of ex vivo cultured DCs is particularly suitable f...…”