The role of dendritic cells as stimulators of minor lymphocyte-stimulating locus-specific T cell responses in the mouse. I. Differential capacity of dendritic cells to stimulate minor lymphocyte-stimulating locus-reactive T cell hybridomas and the primary anti-minor lymphocyte-stimulating locus mixed lymphocyte reaction.
The response of T cells to minor lymphocyte-stimulating locus (Mls) determinants remains poorly understood with respect to the antigenic determinants responsible for T cell stimulation and the types of APC capable of stimulating the response. In this report, we demonstrate that highly purified dendritic cells (DC) as well as B cells have the capacity to stimulate Mls-specific responses. Unseparated spleen cells, purified DC, resting B cells, and activated B cells were compared for their capacity to stimulate several Mls-reactive T cell hybridomas. Whereas the entire panel of Mls-reactive T cell hybridomas was stimulated strongly by unseparated spleen cells and activated B cells, the hybridomas responded only weakly to purified DC or resting B cells. Activation of resting B cells with either B cell stimulatory factor-1 (1 day pre-treatment) or LPS/dextran (2 or 3 day pre-treatment) greatly augmented their Mls-stimulatory capacity. In contrast, the Mls-stimulatory capacity of DC was not augmented by a 1-day pre-treatment with either B cell stimulatory factor-1 or supernatant from the DC-induced primary anti-Mls-MLR. In the primary anti-Mls-MLR, both purified DC and LPS/dextran-stimulated B blasts were found to elicit vigorous T cell proliferative responses. Much weaker responses were elicited by unseparated spleen cells. The stimulation of the primary anti-Mls-MLR by purified DC was further confirmed by producing Mls-specific T cell clones which were preferentially stimulated by DC. Autologous (Mlsb) DC were found to markedly enhance the primary anti-Mls-MLR response to small numbers of Mlsa B blasts. Thus, DC possess other "accessory cell" properties that augment the primary anti-Mls-MLR despite the predicted low level of Mls determinant expression on DC based on the results obtained with Mls-reactive hybridomas. Possible accessory cell properties of DC relevant to this phenomenon are discussed.
Hamilos
D L
DL
Anna Perahia Addato Clinical Research Facilities, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Mascali
J J
JJ
Chesnut
R W
RW
Young
R M
RM
Ishioka
G
G
Grey
H M
HM
D000818:Animals; D000954:Antigens, Surface / Q000145:classification / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology*; D003911:Dextrans; D006825:Hybridomas / Q000276:immunology*; D007399:Interphase; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D016747:Minor Lymphocyte Stimulatory Antigens; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*
D000954:Antigens, Surface; D003911:Dextrans; D008070:Lipopolysaccharides; D016747:Minor Lymphocyte Stimulatory Antigens