Bone marrow microenvironment facilitating dendritic cell: CD4 T cell interactions and maintenance of CD4 memory.
This study shows that bone marrow (BM) stroma expresses constitutively multiple adhesion molecules (ICAM-1, VCAM-1, MadCAM-1, P-selectin) relevant for the homing and infiltration of BM by blood derived T lymphocytes, and also the co-stimulatory molecule CD80, relevant for T cell activation. T cells were capable of homing to BM but not to thymus. Homing to BM involved the integrins LFA-1alpha and alpha4 which interact with the above constitutively expressed cell adhesion molecules (CAMs). CD3 T cells were detected together with BM resident CD11c dendritic cells (DCs), often enriched in follicle-like structures in BM parenchyma. Cognate interactions between transferred antigen specific transgenic CD4 T cells and antigen laden BM-DCs led to formation of multicellular clusters in situ in BM, to generation of lymphoblasts and to clonal T cell expansion within such clusters. The great majority of BM-CD4 T cells had a memory phenotype suggesting that the BM microenvironment facilitates maintenance of CD4 memory. These results extend and corroborate our previous findings on BM-CD8 T cell mediated immune responses. Together these findings suggest that DC-T cell interactions in BM play an important role in immune responses to blood-borne antigen and in the establishment of systemic immunity and long-term memory.
Feuerer
Markus
M
Tumor Immunology Program, German Cancer Research Center, DKFZ, D-69120 Heidelberg, Germany.
Beckhove
Philipp
P
Mahnke
Yolanda
Y
Hommel
Mirja
M
Kyewski
Bruno
B
Hamann
Alf
A
Umansky
Viktor
V
Schirrmacher
Volker
V
D000818:Animals; D017951:Antigen Presentation; D001854:Bone Marrow Cells / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002450:Cell Communication; D002465:Cell Movement; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D007156:Immunologic Memory; D016130:Immunophenotyping; D039441:Integrin alpha4 / Q000502:physiology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL
D016169:Lymphocyte Function-Associated Antigen-1; D039441:Integrin alpha4