PubMed · 7587349
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E Heinen, A Bosseloir, F Bouzahzah. 1995. Follicular dendritic cells: origin and function.. https://doi.org/10.1007/978-3-642-79603-6_2
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Dendritic cells (DC) are potent APC that, in mature form, can be distinguished from other mononuclear cells on the basis of their distinct morphology, absence of lineage markers, and dense expression of MHC and costimulatory molecules. While comparing different DC preparation methods, we observed that DC derived from cultured PBMC that had been depleted of CD2+ cells before culture were functionally distinct from DC derived from PBMC that had not been depleted of CD2+ cells. Thus, both types of DC stimulated allogeneic T cells to proliferate in the MLR, but only DC derived from CD2+ precursors could sensitize naive T cells to soluble Ags such as keyhole limpet hemocyanin and HIV gp160 glycoprotein. Subsequent studies confirmed the existence of CD2+ and CD2- DC precursor populations among HLA-DRbright, lineage-negative PBMC. Immediately after their isolation, these populations were morphologically similar to one another by light and electron microscopy, and neither had substantial Ag-presenting activity. After culture for 24 to 48 h with supernatant from PHA-activated PBMC, both populations developed dendrites, formed clusters with T cells, and stimulated allogeneic T cell responses in the MLR as well as autologous T cell responses to tetanus toxoid, a recall Ag. However, CD2+ DC precursors alone gave rise to APC that presented soluble Ags to naive CD4+ T cells, a property that could be inhibited by Abs to CD4, CD11a, and CD28 on T cells or CD86 on DC. The expression of CD54 and CD86 on CD2+ DC precursors was increased markedly after their culture and differentiation, while the expression of these molecules on CD2- DC precursors was not remarkably changed. These findings reveal the existence of two functionally distinct populations of DC, each derived from a phenotypically distinct precursor present in monocyte-depleted peripheral blood.
Recent investigations in antigen processing suggest that many hematopoietic and nonhematopoietic cell types are capable of presenting alloantigen to T lymphocytes. However, the role of certain nonclassical antigen presenting cells is blurred by their apparent ability to down-regulate the immune response as well as activate immune cells, depending upon the microenvironment and the functional state of the responding cells. In this study we examine the ability of cultured allogeneic keratinocytes to inhibit the response of naive T cells to alloantigen or to anti-CD3. Our results demonstrate that as few as 6.25 x 10(3) keratinocytes significantly inhibited T cell proliferation in response to alloantigen as well as anti-CD3-mediated stimulation (49 and 54%, respectively). HK-mediated inhibition of T cell proliferation did not require cell contact, suggesting that inhibition is mediated by cytokines or other soluble factors. This was further supported by experiments demonstrating the inducibility of HK inhibitory activity in the presence of FCS, and the partial blockage of HK inhibitory activity through the addition of indomethacin or anti-TGFbeta antibody. Interestingly, the data suggest that IL-10, a known immunomodulatory cytokine, does not play a role in the inhibitory activity seen in this system. Taken together the results suggest that HK have the potential to regulate the response of T cells to antigen presented by other APC through the production of soluble factors.
HLA-DM- APC are unable to present soluble Ags to T cells in the context of class II DR molecules. This defect in DM- APC can be overcome by receptor-mediated delivery of Ag into cells. Ag conjugated to ligands for cell surface receptors, such as transferrin or goat anti-human Ig, was processed and presented by DM- T2.DR4 cells. Intracellular processing of Ag conjugates was required, as receptor cross-linking alone did not restore presentation by DM- APC. Ag conjugates targeted by transferrin receptors to endosomes or via surface Ig to endosomal and lysosomal compartments, were each efficiently presented by DM- cells. These Ag conjugates were predominantly localized in light density endosomes in T2.DR4 cells. This study demonstrates that the facilitated uptake and sorting of exogenous Ag by cell surface receptors allow efficient class II-restricted presentation even in the absence of HLA-DM.