Regulation of memory CD4 T-cell pool size and function by natural killer T cells in vivo

Abstract

To develop more effective vaccines and strategies to regulate chronic inflammatory diseases, it is important to understand the mechanisms of immunological memory. Factors regulating memory CD4 + T helper (Th)-cell pool size and function remain unclear, however. We show that activation of type I invariant natural killer T (iNKT) cells with glycolipid ligands and activation of type II natural killer T (NKT) cells with the endogenous ligand sulfatide induced dramatic proliferation and expansion of memory, but not naïve, CD4 T cells. NKT cell-induced proliferation of memory Th1 and Th2 cells was dependent largely on the production of IL-2, with Th2-cell proliferation also affected by loss of IL-4. Type II NKT cells were also required for efficient maintenance of memory CD4 T cells in vivo. Activation of iNKT cells resulted in up-regulation of IFN-γ expression by memory Th2 cells. These IFN-γ-producing memory Th2 cells showed a decreased capability to induce Th2 cytokines and eosinophilic airway inflammation. Thus, activated NKT cells directly regulate memory CD4 T-cell pool size and function via the production of cytokines in vivo.α-galactosylceramide | CD1d KO mice | Jα18 KO mice | STAT5 | allergy

Thy1+IL-7+lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation

“…However, the memory Th2 cells in iBALT in our experimental system were maintained in an IL-7-dependent manner, and by an antigen-independent mechanism. Memory T cells localized in the periphery, particularly at the sites near the mucosal barrier, are likely to be exposed often to stimulants including antigens, ligands for TLR, and cytokines, including those secreted from other lymphocytes (48), and may acquire distinct characteristics from memory T cells maintained in lymphoid organs. In fact, memory Th2 cells proliferate in response to IL-2 and IL-4 produced by invariant natural killer T (iNKT) cells activated with ligands, including a bacterial glycolipid, GSL1, and alter their phenotype to induce type1 inflammation (48).…”

Exposure to allergen and diesel exhaust particles potentiates secondary allergen-specific memory responses, promoting asthma susceptibility

“…Since the nature and size of the effector response influences the nature and size of the memory T-cell pool 16–18 , we hypothesized that the increased accumulation of effector/memory Th2 cells in the lungs of mice co-exposed to HDM plus DEP will result in the persistence of more HDM-specific memory Th2 cells in the lungs upon resolution of the effector Th2 response, potentiating future recall responses. We further hypothesized that if DEP exposure potentiates recall responses to allergen, then early life DEP exposure may promote the development of allergic asthma in children.…”

NKT Cells Determine Titer and Subtype Profile of Virus-Specific IgG Antibodies during Herpes Simplex Virus Infection

“…iNKT cell-dependent production of IgG2a/c and IgG3 subtypes also was observed in a study analyzing the Ab response to a model haptenated lipid molecule (44). Activation of iNKT cells modulates function of Th2 cells in such a way that they produce more IFN-g and less Th2 cytokines (45). This effect could also contribute to production of IgG2a/c and IgG3 during HSV-1 infection.…”

“…In accordance, iNKT cells have been shown to enhance the T cell stimulatory capacity of DCs (54). Finally, iNKT cells may influence Ab production through controlling the maintenance of memory Th cells (45) The iNKT-dependent polarization of the HSV-1-specific B cell response is of biological relevance because HSV-1-specific IgG2a/c Abs exert a more profound neutralizing capacity than HSV-1-specific IgG1 Abs (55). Thus, the lack of a Th1-polarized B cell response could explain the more prominent HSV-1-induced zosteriform lesions and impaired virus clearance that is observed in iNKT cell-deficient mice (13,56).…”