CD40 Ligation In Vivo Induces Bystander Proliferation of Memory Phenotype CD8 T Cells

Abstract

Injection of agonistic anti-CD40 Abs into mice has been shown to amplify weak CD8 T cell responses to poorly immunogenic compounds and to convert T cell tolerance to T cell priming. In this study we demonstrate that anti-CD40 treatment of C57BL/6 mice, without Ag delivery, led to a marked increase in the number of memory phenotype CD4 and CD8 T cells. Adoptive transfer experiments using CD40-deficient hosts further revealed that the proliferative response of memory T cells, induced by systemic CD40 signaling, was dependent on CD40 expression of host APCs. CD40 ligation in vivo induced vigorous cell division of both memory phenotype and bona fide virus-specific memory CD8 T cells in a partially IL-15-dependent manner. However, only memory phenotype, but not Ag-experienced memory CD8 T cells increased in cell number after anti-CD40 treatment in vivo. Taken together our data show that activation of APC via CD40 induces a marked bystander proliferation of memory phenotype T cells. In addition, we demonstrate that bona fide Ag-experienced memory CD8 T cells respond differently to anti-CD40-induced signals than memory phenotype CD8 T cells.

Sialyl lewisx antigen-expressing human CD4+ T and CD8+ T cells as initial immune responders in memory phenotype subsets

“…Many researchers have reported that administration of TLR ligands such as LPS, polyinosinic:polycytidylic acid, and CpG DNA induces proliferation of memory CD8 ϩ T cells through production of cytokines involving type I IFNs, IL-12, IL-15, and IL-18 [5,35]. It was demonstrated that the cytokine-dependent bystander activation was sufficient to induce IFN-␥ production from memory T cells in vivo [6 -8].…”

“…sLe x antigen-expressing and sLe x antigen-negative CD4 ϩ T (A) or CD8 ϩ T (B) cells were isolated by the FACSVantage cell sorting system. The isolated cells (1ϫ10 5 ) were cultured in the presence of IL-2 (20 U/mL) plus IL-15 (20 ng/mL) or IL-12 (50 U/mL) for 3 days. IFN-␥ levels in culture supernatants were determined by ELISA.…”

“…Memory CD4 ϩ T and CD8 ϩ T cells exist in peripheral tissues for long periods and prepare for the next immunological events [1,2]. Several cytokines such as IL-7, IL-12, IL-15, IL-18, IFN-␣/␤, and IFN-␥ contribute to the maintenance of memory CD4 ϩ T and CD8 ϩ T cells, with or without the antigen stimulation through TCR [3][4][5]. Such cytokine-mediated activation of memory T cells is closely related with the early stage of innate immunity against infections [6 -8].…”

Regulation of Th2 Responses and Allergic Inflammation through Bystander Activation of CD8+ T Lymphocytes in Early Life

“…Together with IL-12, CD40 and NKG2D ligation could be involved in the stimulation of memory CD8 + T cells (40)(41)(42). In the present model, we ruled out the involvement of MHC class I recognition (classical or nonclassical MHC class I molecules, such as Qa-1, a MHC-Ib product) in the activity of regulatory CD8 + T cells, because semiallogeneic DC-stimulated CD8 + T cells were able to inhibit Th2 cytokine production and OVA-specific IgE production when transferred to OVA-sensitized b2m-deficient mice.…”

Chronic Leishmania donovani Infection Promotes Bystander CD8 + -T-Cell Expansion and Heterologous Immunity

“…The in vivo regulation of bystander expansion is likely to be both complex and highly dynamic and controlled by cytokines and costimulatory receptor-ligand interactions (4,5,11,13,26), and many of these parameters remain to be fully evaluated in our model. However, it is known that there is increased accumulation of IL-2 mRNA in mice with chronic L. donovani infections (6), and more recent preliminary studies indicate that IL-7 mRNA accumulation was not altered, while IL-15 mRNA accumulation was reduced in the spleens of infected mice compared to the spleens of naïve mice (Polley, unpublished data).…”