Dibutyryl cytidine 3′:5′-cyclic monophosphate; an inhibitor of A23187-stimulated macrophage leukotriene B4 synthesis

db-cCMP inhibits A23187-stimulated TXB2 and LTB4 synthesis by rat carrageenin-elicited peritoneal macrophages in vitro

The European Court and National Courts,Doctrine and Jurisprudence: Legal Change in its Social Context,Report on Italy

Digitised version produced by the EUI Library and made available online in 2020

Activated T cells recruit exosomes secreted by dendritic cells via LFA-1

Contains fulltext : 79542.pdf (publisher's version ) (Closed access)Dendritic cells (DCs) are known to secrete exosomes that transfer membrane proteins, like major histocompatibility complex class II, to other DCs. Intercellular transfer of membrane proteins is also observed during cognate interactions between DCs and CD4(+) T cells. The acquired proteins are functional and play a role in regulation of immune responses. How membrane protein transfer is achieved and regulated is unclear. Here we show that T cells can recruit major histocompatibility complex class II-containing DC exosomes secreted in the extracellular milieu during cognate DC-T-cell interactions. Recruitment of these exosomes required T-cell activation and was dependent on leukocyte function-associated antigen-1 (LFA-1) rather than on T-cell receptor specificity. Indeed, inducing a high-affinity state of LFA-1 on resting T cells was sufficient to provoke exosome binding. These results imply that DC exosomes secreted in the extracellular milieu during cognate T-cell-DC interactions are targeted to T cells activated in that microenvironment

Split T Cell Tolerance against a Self/Tumor Antigen: Spontaneous CD4+ but Not CD8+ T Cell Responses against p53 in Cancer Patients and Healthy Donors

Analyses of NY-ESO-1-specific spontaneous immune responses in cancer patients revealed that antibody and both CD4+ and CD8+ T cell responses were induced together in cancer patients. To explore whether such integrated immune responses are also spontaneously induced for other tumor antigens, we have evaluated antibody and T cell responses against self/tumor antigen p53 in ovarian cancer patients and healthy individuals. We found that 21% (64/298) of ovarian cancer patients but no healthy donors showed specific IgG responses against wild-type p53 protein. While none of 12 patients with high titer p53 antibody showed spontaneous p53-specific CD8+ T cell responses following a single in vitro sensitization, significant p53-specific IFN-γ producing CD4+ T cells were detected in 6 patients. Surprisingly, similar levels of p53-specific CD4+ T cells but not CD8+ T cells were also detected in 5/10 seronegative cancer patients and 9/12 healthy donors. Importantly, p53-specific CD4+ T cells in healthy donors originated from a CD45RA− antigen-experienced T cell population and recognized naturally processed wild-type p53 protein. These results raise the possibility that p53-specific CD4+ T cells reflect abnormalities in p53 occurring in normal individuals and that they may play a role in processes of immunosurveillance or immunoregulation of p53-related neoplastic events