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antigen presenting cell, cell function, cytotoxic t lymphocyte, dendritic cell, influenza virus, protein synthesis, spleen cell, t lymphocyte, ultraviolet irradiation, virus replication


We have evaluated the capacity of dendritic ceUs to function as antigen-presenting cells (APCs) for influenza and have examined their mechanism of action. Virus-pulsed dendritic cells were 100 times more efficent than bulk spleen ceUs in stimulating cytotoxic T lymphocyte (CTL) formation. The induction of CTLs required neither exogenous lymphokines nor APCs in the responding T cell population. Infectious virus entered dendritic cells through intraceUular acidic vacuoles and directed the synthesis of several viral proteins. If ultravidet (UV)-inactivated or bromdain-treated viruses were used, viral protein synthesis could not be detected, and there was poor induction of CTLs. This indicated that dendritic cells were not capable of processing noninfectious virus onto major histocompatibility complex (MHC) class I molecules. However, UV-inactivated and bromdain-treated viruses were presented efficently to class II-restricted CD4+ T ceils. The CD4+ T cells crossreacted with different strains of influenza and markedly amplified CTL formation. Cell lines that lacked MHC class II, and consequently the capacity to stimulate CD4+ T cells, failed to induce CTLs unless hdper lymphokines were added. Similarly, dendritic cells pulsed with the MHC class I-restricted nucleoprotdn 147-155 peptide were poor stimulators in the absence of exogenous hdper factors. We condude that the function of dendritic cells as APCs for the generation of virus-spedfic CTLs in vitro depends measurably upon: (a) charging class I molecules with peptides derived from endogenously synthesized viral antigens, and (b) stimulating a strong CD4+ helper T cell response.


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