Common causes for unsatisfactory Pap tests in a high-risk population: insights into a yet unresolved problem in gynecologic cytology.

Introduction: Although the rates are generally low (0.2%-10%), unsatisfactory Papanicolaou (Pap) tests are associated with an increased risk of epithelial lesions on subsequent follow-up. Therefore, some studies have recommended extra laboratory processing, resampling of patients, and more recently, human papillomavirus testing.

Gld mutation of Fas ligand increases the frequency and up-regulates cell survival genes in CD25+CD4+ TR cells.

The Fas pathway and regulatory T (T(R)) cells play intertwining roles in controlling T cell tolerance through deletion and suppression of autoreactive T cells. Impairment of either mechanism causes severe T cell lymphoproliferation albeit with opposing outcomes. T cell lymphoproliferation induced by defective Fas pathway does not cause overt lymphocytic infiltration but rather prevents an important set of T cell-mediated autoimmune diseases.

B220+ double-negative T cells suppress polyclonal T cell activation by a Fas-independent mechanism that involves inhibition of IL-2 production.

Fas-mediated apoptosis is a key mechanism for elimination of autoreactive T cells, yet loss of function mutations in the Fas signaling pathway does not result in overt T cell-mediated autoimmunity. Furthermore, mice and humans with homozygous Fas(lpr) or Fas ligand(gld) mutations develop significant numbers of B220+ CD4- CD8- double-negative (DN) alphabeta T cells (hereafter referred to as B220+ DN T cells) of poorly understood function. In this study, we show that B220+ DN T cells, whether generated in vitro or isolated from mutant mice, can suppress the ability of activated T cells to proliferate or produce IL-2, IL-10, and IFN-gamma.