Antigen-specific T lymphocytes efficiently cluster with dendritic cells in the human primary mixed-leukocyte reaction.
Experimental conditions have been developed to detect the efficient interaction of antigen-presenting cells and antigen-specific CD4+ T lymphocytes early in the human primary mixed-leukocyte reaction (MLR). When monocytes are depleted from the stimulator population, it is evident that small numbers of allogeneic dendritic cells form multicellular aggregates with responsive T cells. B cells and monocytes in allogeneic stimulator populations do not appear to form aggregates in the first 2 days of the MLR. Upon return to culture, most of the lymphocytes that have clustered with dendritic cells become IL-2 responsive, proliferating lymphoblasts. The nonclustered cells exhibit little growth, while mixtures of clusters and nonclusters proliferate comparably to clusters alone. Cluster-derived lymphocytes respond rapidly to rechallenge with foreign leukocytes from the original donor but are greater than 90% depleted of reactivity to other "third party" donors. Nonclustered lymphocytes, in contrast, are greater than 90% depleted in specific reactivity but respond normally to third party. Therefore antigen-specific (alloreactive) resting CD4+ lymphocytes efficiently and selectively aggregate with dendritic cells. Dendritic-T-cell aggregates represent a stable microenvironment in which the MLR begins and might be useful in the experimental analysis of early events in the sensitization phase of cell-mediated immunity in man.
D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002448:Cell Adhesion; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology*; D006801:Humans; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D007959:Lymphocyte Culture Test, Mixed; D008855:Microscopy, Electron, Scanning; D013601:T-Lymphocytes / Q000166:cytology*; D013997:Time Factors
D000911:Antibodies, Monoclonal