Transfer of antigen between dendritic cells in the stimulation of primary T cell proliferation

Abstract

Primary proliferative T cell responses require stimulation with antigen-pulsed dendritic cells (Ag-DC). Here we show that for optimal stimulation, dendritic cells (DC) not exposed directly to antigen are also required. Ag-DC added to DC-depleted T cells caused negligible primary stimulation; adding back DC resulted in stimulation. These effects were seen using the contact sensitizer fluorescein isothiocyanate (FITC), FITC conjugated to ovalbumin (FITC-OVA) or influenza virus as antigens. DC co-cultured with Ag-DC (using FITC or FITC-OVA) acquired antigen indicating that antigen was transferred between DC. DC that acquired antigen secondarily were separated by cell sorting and stimulated primary T cell proliferation directly. DC were also pulsed with FITC, washed thoroughly and incubated overnight. Supernatants contained shed antigen since DC incubated in these supernatants acquired antigen as indicated by flow cytometry. DC acquiring the shed antigen also stimulated T cell proliferation although the stimulation was not as effective as that seen when cell contact between DC and antigen-bearing DC occurred. Thus, in primary stimulation, activation of T cells may occur when there is an antigen gradient between Ag-DC and DC and the mechanisms underlying these effects are now being sought. We propose that this unique interaction between antigen-presenting cells may be a paradigm for self/non-self discrimination.

Efficient nonviral transfection of dendritic cells and their use for in vivo immunization

“…The proportion of DCs presenting antigen may exceed this figure, partly because DCs expressing antigen genes at undetectable levels can stimulate antigen-specific T-cell responses 14 , and partly because antigen may be transferred readily from DCs producing it endogenously to other DCs (ref. 23). Our results with human DCs showed that CL22 transfection enabled the hmoDCs to stimulate in vitro expansion and activation of antigen-specific, autologous CD8 + T cells for recall antigens, allowing detection of their lytic activity on target cells.…”

B Cells Activated in Lymph Nodes in Response to Ultraviolet Irradiation or by Interleukin-10 Inhibit Dendritic Cell Induction of Immunity

“…To verify that any changes were independent of the antigen used, a different contact antigen (FITC) was used in separate experiments. The method used to conjugate FITC to APC in vitro was similar to that above and has been described elsewhere (Knight et al, 1998).…”

Recent advances in mastocytosis and neoplasms of probable monocytic/dendritic cell lineage

“…49 It is likely that interdigitating dendritic cells are simply interstitial dendritic cells (see below) and Langerhans cells that have migrated to the lymph node from peripheral tissues and undergone maturation ( Figure 5), although some authors suggest that they may be a separate DC population to which antigen is passed by DCs migrating from peripheral tissues. 49,50 Interstitial dendritic cells and macrophages: prior to immunohistochemistry, the poorly defined term ''histiocyte'' referred to a cell with macrophage or epidermal Langerhans cell morphology. 10,40,51,52 Subsequently, ''histiocyte'' referred to cells that were CD68þ.…”