It is well established that CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) play a crucial role in the course of different infectious diseases. However, contradictory results have been published regarding to malaria infection. In this study, we report that specific ablation of Foxp3(+) Tregs in Plasmodium yoelii-infected DEREG-BALB/c mice leads to an increase in T cell activation accompanied b...

CTLA-4 is thought to inhibit effector T cells both intrinsically, by competing with CD28 for B7 ligands, and extrinsically, through the action of regulatory T cells (Tregs). We studied in vivo responses of normal and CTLA-4-deficient Ag-specific murine effector CD4(+) T cells. We directly demonstrate that effector T cell-restricted CTLA-4 inhibits T cell responses in a cell-extrinsic manner. Co...

CD40 stimulation on antigen-presenting cells (APC) allows direct activation of CD8(+) cytotoxic T cells, independent of CD4⁺ T-cell help. Agonistic anti-CD40 antibodies have been demonstrated to induce beneficial antitumor T-cell responses in mouse models of cancer and early clinical trials. We report here that anti-CD40 treatment induces programmed death ligand-1 (PD-L1) upregulation on tumor-...

Studies in malaria patients indicate that higher frequencies of peripheral blood CD4(+) Foxp3(+) CD25(+) regulatory T (Treg) cells correlate with increased blood parasitemia. This observation implies that Treg cells impair pathogen clearance and thus may be detrimental to the host during infection. In C57BL/6 mice infected with Plasmodium berghei ANKA, depletion of Foxp3(+) cells did not improv...

CTLA-4: cytotoxic T-lymphocyteeassociated antigen 4 irAEs: immune-related adverse events PD-1: programmed deathe

Melanoma patients treated with anti-CTLA-4 have shown a range of anti-tumor responses. In this report, we describe the response of a single patient to anti-CTLA-4, with individual lesions disappearing, others stabilizing, and others progressing. These responses can be viewed as a clear manifestation of cancer immunoediting and its three phases of elimination, equilibrium and escape, with each t...

We present a theoretical framework for simulating the synaptic accumulation of the costimulatory molecules CD28, CTLA-4, B7-1, and B7-2, based on a system of mean-field, ordinary differential equations, and rigorous biophysical and expression data. The simulations show that binding affinity, stoichiometric properties, expression levels, and, in particular, competition effects all profoundly inf...

As a potential founder population of MS, the Scandinavian ethnic group is of special interest in MS genetics. Project in these countries have recently led to several reports, including associations with HLA class I, CTLA-4 and suggestive linkage to several chromosomal candidate loci. The analysis of isolated populations within Scandinavia may also prove to be rewarding.

We have derived from lymphocytes infiltrating a human regressive melanoma lesion a series of T-cell receptor alpha/beta-dependent, HLA-B14-restricted cytotoxic T-lymphocyte clones reactive against the autologous tumor. Analysis of the T-cell receptor gene expression revealed that all the clones represented a unique cell expressing a V beta 13.1/J beta 1.1 gene segment. T-cell receptor transcrip...