In vivo detection of dendritic cell antigen presentation to CD4(+) T cells

被引:452
作者
Ingulli, E
Mondino, A
Khoruts, A
Jenkins, MK
机构
[1] UNIV MINNESOTA,SCH MED,DEPT MICROBIOL,MINNEAPOLIS,MN 55455
[2] UNIV MINNESOTA,SCH MED,CTR IMMUNOL,MINNEAPOLIS,MN 55455
基金
英国惠康基金;
关键词
D O I
10.1084/jem.185.12.2133
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Although lymphoid dendritic cells (DC) are thought to play an essential role in T cell activation, the initial physical interaction between antigen-bearing DC and antigen-specific T cells has never been directly observed in vivo under conditions where the specificity of the responding T cells for the relevant antigen could be unambiguously assessed. We used confocal microscopy to track the in vivo location of fluorescent dye-labeled DC and naive TCR transgenic CD4(+) T cells specific for an OVA peptide-I-A(d) complex after adoptive transfer into syngeneic recipients. DC that were not exposed to the OVA peptide, homed to the paracortical regions of the lymph nodes but did not interact with the OVA peptide-specific T cells. In contrast, the OVA peptide-specific T cells formed large clusters around paracortical DC that were pulsed in vitro with the OVA peptide before injection. Interactions were also observed between paracortical DC of the recipient and OVA peptide-specific T cells after administration of intact OVA. Injection of OVA peptide-pulsed DC caused the specific T cells to produce IL-2 in vivo, proliferate, and differentiate into effector cells capable of causing a delayed-type hypersensitivity reaction. Surprisingly, by 48 h after injection, OVA peptide-pulsed, but not unpulsed DC disappeared from the lymph nodes of mice that contained the transferred TCR transgenic population. These results demonstrate that antigen-bearing DC directly interact with naive antigen-specific T cells within the T cell-rich regions of lymph nodes. This interaction results in T cell activation and disappearance of the DC.
引用
收藏
页码:2133 / 2141
页数:9
相关论文
共 27 条
[1]   FLOW CYTOMETRIC DETERMINATION OF CYTOKINES IN ACTIVATED MURINE T-HELPER LYMPHOCYTES - EXPRESSION OF INTERLEUKIN-10 IN INTERFERON-GAMMA AND IN INTERLEUKIN-4-EXPRESSING CELLS [J].
ASSENMACHER, M ;
SCHMITZ, J ;
RADBRUCH, A .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1994, 24 (05) :1097-1101
[2]  
AUSTYN JM, 1988, IMMUNOLOGY, V63, P691
[3]  
BRELJE TC, 1993, METHOD CELL BIOL, V38, P97
[4]   Regulation of dendritic cell numbers and maturation by lipopolysaccharide in vivo [J].
DeSmedt, T ;
Pajak, B ;
Muraille, E ;
Lespagnard, L ;
Heinen, E ;
DeBaetselier, P ;
Urbain, J ;
Leo, O ;
Moser, M .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (04) :1413-1424
[5]   T-CELL RECEPTOR CROSS-LINKING TRANSIENTLY STIMULATES ADHESIVENESS THROUGH LFA-1 [J].
DUSTIN, ML ;
SPRINGER, TA .
NATURE, 1989, 341 (6243) :619-624
[6]   ANTIGEN-SPECIFIC LYMPHOCYTES-T EFFICIENTLY CLUSTER WITH DENDRITIC CELLS IN THE HUMAN PRIMARY MIXED-LEUKOCYTE REACTION [J].
FLECHNER, ER ;
FREUDENTHAL, PS ;
KAPLAN, G ;
STEINMAN, RM .
CELLULAR IMMUNOLOGY, 1988, 111 (01) :183-195
[7]   THE MAJOR HISTOCOMPATIBILITY COMPLEX-RESTRICTED ANTIGEN RECEPTOR ON T-CELLS .1. ISOLATION WITH A MONOCLONAL-ANTIBODY [J].
HASKINS, K ;
KUBO, R ;
WHITE, J ;
PIGEON, M ;
KAPPLER, J ;
MARRACK, P .
JOURNAL OF EXPERIMENTAL MEDICINE, 1983, 157 (04) :1149-1169
[8]   GENERATION OF LARGE NUMBERS OF DENDRITIC CELLS FROM MOUSE BONE-MARROW CULTURES SUPPLEMENTED WITH GRANULOCYTE MACROPHAGE COLONY-STIMULATING FACTOR [J].
INABA, K ;
INABA, M ;
ROMANI, N ;
AYA, H ;
DEGUCHI, M ;
IKEHARA, S ;
MURAMATSU, S ;
STEINMAN, RM .
JOURNAL OF EXPERIMENTAL MEDICINE, 1992, 176 (06) :1693-1702
[9]   CLUSTERING OF DENDRITIC CELLS, HELPER-T, LYMPHOCYTES-T, AND HISTOCOMPATIBLE B-CELLS DURING PRIMARY ANTIBODY-RESPONSES INVITRO [J].
INABA, K ;
WITMER, MD ;
STEINMAN, RM .
JOURNAL OF EXPERIMENTAL MEDICINE, 1984, 160 (03) :858-876
[10]   ACCESSORY CELL LYMPHOCYTE-T INTERACTIONS - ANTIGEN-DEPENDENT AND ANTIGEN-INDEPENDENT CLUSTERING [J].
INABA, K ;
STEINMAN, RM .
JOURNAL OF EXPERIMENTAL MEDICINE, 1986, 163 (02) :247-261