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Cytotoxic Pathway (cytotoxic + pathway)
Selected Abstracts,,, T cells inhibit in vitro growth of the asexual blood stages of Plasmodium falciparum by a granule exocytosis-dependent cytotoxic pathway that requires granulysinEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2004Salah Abstract Several reports have stated the ability of ,,, T cells to inhibit the growth of the asexual blood stages of Plasmodium falciparumin vitro. However, little information is available about the mechanisms involved. In this study, in vitro systems were used to study the role of the granule exocytosis-dependent cytotoxic pathway in the growth inhibition/killing of P. falciparum by human ,,, T cells. Our results show that the inhibition requires cell-to-cell contact and that ,,, T cells kill the asexual blood stages of P. falciparum through a granule exocytosis-dependent cytotoxic pathway after recognition of certain ligands or molecules expressed on the surface of infected erythrocytes or merozoites. The in vitro inhibitory capacity of ,,, T cells was strongly correlated with the expression of granulysin in the cytotoxic granules, while non-inhibitory CD4+ and CD8+ T cells expressed very little, implicating a role for granulysin in parasite inhibition. This was further suggested by the addition of neutralizing anti-granulysin antibodies, which abrogated the parasite inhibitory capacity of the ,,, T cells. Taken together, our results suggest that the capacity of ,,, T cells for inhibition/killing of P. falciparum is based on the granule exocytosis-dependent cytotoxic pathway and that the presence of granulysin is essential to maintain efficient killing. [source] Evidence for a perforin-mediated mechanism controlling cardiac inflammation in Trypanosoma cruzi infectionINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 2 2002ANDREA HENRIQUES-PONS Summary. ,CD8+ T lymphocytes are considered an important cell population involved in the control of parasitaemia and mortality after Trypanosoma cruzi infection. However, despite recent developments in this field, the mechanism whereby this control is exerted is still not completely understood. Here we have used perforin knockout (,/,) mice infected with Y strain T. cruzi in order to evaluate specifically the participation of the perforin-based cytotoxic pathway in the destruction of cardiomyocytes, cellular inflammatory infiltration, and control of parasitaemia and mortality. We observed that although parasitaemia was equivalent in perforin (+/+) and (,/,) groups, survival rate and spontaneous physical performance were significantly lower in the perforin deficient mice. The cardiac inflammatory cell infiltration, mostly composed of CD8+ cells, was more evident in perforin (,/,) mice. Ultrastructural and immunofluorescence analysis, as well as plasma creatine kinase activity, revealed cardiomyocyte damage and necrosis, more evident in perforin (,/,) mice. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assays performed in heart samples revealed similar and modest levels of apoptosis in both perforin (+/+) and (,/,) mice. These results indicate that perforin does not play a pivotal role in the control of parasitaemia and direct lysis of cardiomyocytes, but seems to be an important molecule involved in the control of cardiac inflammation and pathology induced by a highly virulent strain of T. cruzi. [source] Islet Allograft Rejection by Contact-Dependent CD8+ T cells: Perforin and FasL Play Alternate but Obligatory Roles,AMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2007M. Sleater Though CD8+ T lymphocytes are important cellular mediators of islet allograft rejection, their molecular mechanism of rejection remains unidentified. Surprisingly, while it is generally assumed that CD8+ T cells require classic cytotoxic mechanisms to kill grafts in vivo, neither perforin nor FasL (CD95L) are required for acute islet allograft rejection. Thus, it is unclear whether such contact-dependent cytotoxic pathways play an essential role in islet rejection. Moreover, both perforin and CD95L have been implicated in playing roles in peripheral tolerance, further obscuring the role of these effector pathways in rejection. Therefore, we determined whether perforin and/or FasL (CD95L) were required by donor MHC-restricted (,direct') CD8+ T cells to reject islet allografts in vivo. Islet allograft rejection by primed, alloreactive CD8+ T cells was examined independently of other lymphocyte subpopulations via adoptive transfer studies. Individual disruption of T-cell-derived perforin or allograft Fas expression had limited impact on graft rejection. However, simultaneous disruption of both pathways prevented allograft rejection in most recipients despite the chronic persistence of transferred T cells at the graft site. Thus, while there are clearly multiple cellular pathways of allograft rejection, perforin and FasL comprise alternate and necessary routes of acute CD8+ T-cell-mediated islet allograft rejection. [source] | ||||||||||