Fas antigen is the major target molecule for CD4+ T cell-mediated cytotoxicity.

Abstract

Activation of the Fas cell surface molecule, either by specific antibody or by its as yet unidentified ligand, has been shown to induce apoptosis. Because apoptosis is also evoked in target cells by cytolytic T cells, we investigated whether the Fas pathway is involved in CD4+ T cell-mediated cytotoxicity. Analysis of Fas expression in APC, such as the B lymphoma A20.2J and MHC class II-transfected fibroblasts RT2.3, revealed a correlation between the degree of expression and sensitivity to cytotoxic attack, high level of Fas expression in A20.2J being associated with efficient lysis. To examine whether increased Fas expression in RT2.3 would render these cells more susceptible to CD4+ CTL lysis, they were transfected with a Fas gene expression vector. Indeed, Fas- but not mock-transfected RT2.3 proved to be more sensitive to lysis by either Ag specifically or nonspecifically activated CD4+ CTL. Similarly, MHC class II-negative, Fas-transfected L1210 leukemia cells were lysed with nonspecifically activated CD4+ CTL. The importance of the Fas engagement in CD4+ CTL-mediated cytotoxicity is further substantiated by the failure of both cloned and normal CD4+ CTL to lyse B cell blasts from Ipr mice. These mice are known to have a defect in functional Fas expression. Although the bulk of CD4+ T cell-mediated lysis appears to be Fas induced, the fact that the effector phase of A20.2J lysis is only partially Ca2+ independent indicates that other pathways also contribute to target cell death.

Cluster of differentiation antigens: essential roles in the identification of teleost fish T lymphocytes

“…Furthermore, it has been shown that the CD4 + T cells in carp ( Carassius auratus langsdorfii ) have strong direct antibacterial activity (Nayak and Nakanishi 2013 ). In mammals, CD4 + Tc cells have also been investigated, and they were found to function using the same cytolytic pathways as those in CD8 + Tc cells (Appay et al 2002 ; Hashimoto et al 2019 ; Stalder et al 1994 ; Williams and Engelhard 1996 ). However, the precise roles of CD4 + Tc cells remain unclear.…”

Avaliação do estado de ativação e da produção de moleculas citotoxicas por linfocitos (CD4+ e CD8+) do sangue periferico de pacientes com paracoccidioidomicose

“…As células T CD4 + atuam classicamente como reguladoras e efetoras da resposta imune a patógenos por meio da produção de citocinas, entretanto há mais de duas décadas têm sido descrito a seu importante papel na resposta citotóxica, tanto em camundongos quanto em humanos contra aloantígenos, células infectadas por microrganismos e células cancerígenas Kresnky et al, 1982;Lewinsohn et al, 1998b;Lukacher et al, 1985;McCarthy et al, 1986;Paludan et al, 2002). Os primeiros estudos mostraram que as células T CD4 + citotóxicas agiam preferencialmente pela interação CD95/CD95L (Hanabuchi et al, 1994;Ju et al 1994;Stalder et al, 1994;Williamns e Engelhard, 1996). Entretanto posteriormente foi demonstrado células CD4 + citotóxicas também utilizam a perforina e a exocitose de granzimas (Hahn et al, 1999;Williams e Engelhard, 1997).…”