Accessory cell-T lymphocyte interactions. Antigen-dependent and -independent clustering.
Previous work documented the capacity of dendritic cells (DC) to stimulate primary immune responses and to physically cluster with the responding lymphocytes. Rapid cell-cell aggregation assays were used here to study the interaction of DC and other types of APC with T lymphocytes. Graded doses of APC were sedimented with T cells that had been primed to alloantigens, soluble proteins, or lectin, and then labeled with carboxyfluorescein diacetate. The number of clustered T cells was measured after 10 min at 4 or 37 degrees C. At 4 degrees, binding was antigen-dependent and included greater than 50% of the added T cells. Clustering was mediated by all types of APC tested, including DC, macrophages, B lymphocytes, and fresh Langerhans cells, although DC were the most effective. Specificity was evident in the findings that alloreactive T lymphoblasts bound to allogeneic but not syngeneic APC; KLH- and OVA-reactive T cells bound to syngeneic APC in the presence of specific protein: and Con A blasts needed lectin to cluster. A 30 min pretreatment with chloroquine, a drug known to inhibit APC activity, markedly blocked the specific binding of alloreactive and protein-specific T blasts at 4 degrees C. Since Lyt-2- alloreactive blasts should specifically recognize Ia, presentation of Ia seems to be altered by chloroquine. Binding assays at 37 degrees C gave similar results to those performed at 4 degrees C, with one exception. When DC were used as APC, striking antigen-independent clustering occurred. DC could efficiently cluster primed T cells in the absence of alloantigen, soluble protein, or lectin. We suggest that antigen-independent binding contributes to the distinctive capacity of DC to prime T cells in the afferent limb of the immune response, whereas antigen-dependent binding between other APC and sensitized lymphocytes is critical in the efferent limb.
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D002449:Cell Aggregation; D002455:Cell Division; D002738:Chloroquine / Q000494:pharmacology; D000078404:Epidermal Cells; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D007519:Isoantigens; D002738:Chloroquine