Role of anti-CD3 in modulation of Th1-type immune response in Shigella dysenteriae infection

Abstract

A murine model was used to evaluate the role of anti-CD3 in modulating a Th1-type response by restimulation of T-cells after immunization with the 57 kDa immunodominant antigen of Shigella dysenteriae 1 outer-membrane proteins (OMPs), followed by Shigella infection after immunization. To observe the effect of anti-CD3, other T-cell cultures were also established following anti-CD1, anti-IL2 and phytohaemagglutinin stimulation. Anti-CD3 stimulation of reconstituted T-cells showed 'mean' levels of CD4 and CD25 were enhanced by 34 . 5 and 31 . 1 % in immunized mice, which was comparable to 53 . 2 and 50 . 7 %, respectively, in challenged-immunized mice, and were dominant over CD8þ T-cells. Levels of IL2 generated by anti-CD3-stimulated T-cells of immunized mice were greater than those of unstimulated T-cells and were significantly elevated in challenged-immunized mice. The reactivity of T-cells indicated their complete responsiveness, as anti-CD3 antibody might not inhibit the migration of the macrophages but rather inhibit IL4. These macrophage factors synergistically act with anions towards an activated response, which in turn provokes IL2 secretion with a low degree of internalization of its receptor. Thus, sharing of IL2 to form a high-affinity receptor complex with CD4

Host Receptor Immunomodulation in Response to <i>Shigella</i> Surface Antigens: An Insight for Vaccine Development

“…There have been several reports on polyclonal T-cell activators like anti-CD1, anti-CD2, anti-CD3 and anti-IL-2 which are often used either to induce lymphoid cell proliferation or cytokine secretion (Moreno-Lafont et al, 2003;Nguyen et al, 1995;Sieling et al, 1995;Sinha and Bagchi, 2004). Anti-CD3 (TCR ligand) identified on T-cell subsets has been not only known to activate and induce memory T-cell but also shown to promote the synthesis of new cytokines (Sinha and Bagchi, 2004). It is also known that activated memory T-cells play an important role in mediating antigen specific response to bacteria.…”

“…It is also known that activated memory T-cells play an important role in mediating antigen specific response to bacteria. In addition, memory T-cells have been shown to determine IFN-γ levels which strongly reflects their role in regulation of Th1 cytokines (Bagchi et al, 2010a;Sinha and Bagchi, 2004). Activation of TCRs by TCR ligand or OX40 ligand (a co-stimulator of Th1-cell) contributes to maintain effector T-cell function as well as to develop memory against antigen-specific stimulation (Bagchi et al, 2010a;Maxwell et al, 2000) via activation of anti-apoptotic Bcl-xl expression of Bcl-2 family proteins (Rogers et al, 2001).…”

“…During maturation and activation of TCR, IL-2R expressed on T-cell is required for IL-2 growth factors via co-receptor molecule such as CD28 leading to IL-2 and IFN-γ secretion towards the cellular target. In the presence of co-stimulatory signals, TCR ligands may also activate memory T-cells via TCR activation (Bagchi and Sinha, 2005;Sinha and Bagchi, 2004). Conversely, in the absence of these signals, TCR cells develop tolerance (Barrett et al, 1993).…”

“…TCR activation by anti-CD3 ligand stimulation in murine Tcells has been shown to induce IL-2 secretory T-cells and requires co-stimulatory signals for further activation and proliferation of memory T-regulatory cells (Moreno-Lafont et al, 2003;Sinha and Bagchi, 2004). T-cell activation up-regulates protein kinase-Cmediated phosphorylation in CD4 + T-cells which enhances IL-2 production, lipid peroxidation as well as formation of reactive oxygen species (ROS) (Bagchi and Sinha, 2005;Sinha and Bagchi, 2004). Increased production of IL-2 enhances its receptor (CD25) activation on macrophages (Sinha and Bagchi, 2004).…”

“…T-cell activation up-regulates protein kinase-Cmediated phosphorylation in CD4 + T-cells which enhances IL-2 production, lipid peroxidation as well as formation of reactive oxygen species (ROS) (Bagchi and Sinha, 2005;Sinha and Bagchi, 2004). Increased production of IL-2 enhances its receptor (CD25) activation on macrophages (Sinha and Bagchi, 2004). The ligand-induced TCR activation might suppress the naïve or memory CD8 + T-cells resulting in CD4 + T-cell selection (Bagchi et al, 2010b).…”