Most T cells belong to either of two lineages defined by the mutually exclusive expression of CD4 and CD8 coreceptors: CD4 T cells are major histocompatibility complex (MHC) II restricted and have helper function, whereas CD8 T cells are MHC I restricted and have cytotoxic function. The divergence between these two lineages occurs during intrathymic selection and is thought to be irreversible i...

Two models have been proposed to explain the requirement for CD40 signaling in CD8 T cell responses. The first model suggests that CD4 T cells activate antigen-presenting cells (APCs) through CD40 signaling (APC licensing). In turn, licensed APCs are able to prime naive CD8 T cells. The second model suggests that CD154-expressing CD4 T cells activate CD40-bearing CD8 T cells directly. Although ...

Thymocytes must bind major histocompatibility complex (MHC) proteins on thymic epithelial cells in order to mature into either CD8+ cytotoxic T cells or CD4+ helper T cells. Thymic precursors express both CD8 and CD4, and it has been suggested that the intracellular signals generated by CD8 or CD4 binding to class I or II MHC, respectively, might influence the fate of uncommitted cells. Here we...

Background: Although there is a growing consensus that hydroxychloroquine may not be effective in the treatment of COVID-19 patients, still little high-quality evidence about prophylactic effects this medication. In study, we aimed to evaluate efficiency preventing infection among healthcare workers. Methods: clinical trial, 90 providers from two referral hospitals were divided into group (400 ...

OBJECTIVE To evaluate the effect of dimethyl fumarate (DMF; Tecfidera, Biogen, Weston, MA) on CD4(+) and CD8(+) T cell subsets in patients with multiple sclerosis (MS). METHODS Peripheral lymphocyte subsets, including CD4(+) and CD8(+) memory cells and T helper (TH) cells TH1, TH2, TH17, and peripheral regulatory T cell (pTreg) subpopulations were analyzed before and 6 months after onset of D...

We generated 1,090 ATAC-seq and 1,057 T-cell RNA-seq libraries from 153 subjects, derived 8 flow-sorted subsets (defined by CD4/CD8, CLA+/ CLA-, 0/24h CD3/CD28 stimulation). Effects of activation skin-homing were analyzed DESeq2. After peak calling, 78,234 consensus peaks present in ≥ 30 libraries. A Wald test examining simple main effects identified 9,072, 3,934, 21,174 as differentially acces...

We investigated whether oral tolerance could block the development of an inflammatory response mediated by CD8+ T cells, using a mouse model of oral tolerance of contact sensitivity (CS) to the hapten 2, 4-dinitrofluorobenzene (DNFB). In this system, the skin inflammatory response is initiated by hapten-specific class I-restricted cytotoxic CD8+ T (CTL) cells, independently of CD4 help. Oral de...

Mice deficient in OX40 or 4-1BB costimulatory pathways show defects in T cell recall responses, with predominant effects on CD4 vs CD8 T cells, respectively. However, OX40L can also stimulate CD8 T cells and 4-1BBL can influence CD4 T cells, raising the possibility of redundancy between the two TNFR family costimulators. To test this possibility, we generated mice deficient in both 4-1BBL and O...

It has been established that insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice results from a CD4+ and CD8+ T cell-dependent autoimmune process directed against the pancreatic beta cells. The precise roles that beta cell-reactive CD8+ and CD4+ T cells play in the disease process, however, remain ill defined. Here we have investigated whether naive beta cell-specific CD8...

BACKGROUND CD8(+) T-cell activation, characterized by increased CD28 expression, reduces neointima formation after arterial injury in mice. The CD8(+)CD28(hi) phenotype is associated with increased effector function. In this study, we used a mouse model that has CD8(+) but no CD4(+) T cells (CD4-/-) to assess the role of CD8(+) T cells and test the function of CD8(+)CD28(hi) T cells in modulati...