Bone marrow can function as a lymphoid organ during a primary immune response under conditions of disrupted lymphocyte trafficking.
In this study we sought to better understand lymphocyte trafficking patterns and the function of secondary lymphoid organs, such as the spleen, during the generation of virus-specific T cell precursors. Treatment of mice with the Mel-14 mAb to CD62L, the lymph node homing receptor, limits trafficking of naive T cells into lymph nodes through high endothelial venules. Administering Mel-14 following respiratory infection with influenza virus forced the generation of primary virus-specific CD4+ and CD8+ T cell precursors from the mediastinal lymph nodes to the spleen. However, splenectomy did not seriously impede virus clearance from the lung and, despite a substantial reduction of the total lymphocyte pool, the acute T cell responses in the regional lymph nodes were largely normal. Mel-14 treatment of splenectomized mice did not affect clonal expansion of the virus-specific T cells in the MLN, while the response in the cervical lymph nodes was still greatly inhibited. More surprisingly, virus-specific T cell precursors were now detected from days 5 to 6 after infection in the bone marrow (BM) of the splenectomized, Mel-14-treated mice. This was not due to contamination with circulating T cells or infection of BM cells because the distribution profiles of precursor T cells for PBL and BM diverged and PCR analysis showed no evidence of virus replication in the BM. It appears that, under these conditions of disrupted lymphocyte trafficking, the BM can supplant the secondary lymphoid tissue either as a site of primary immune response or as a cache for excess T cell precursors.
Tripp
R A
RA
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Topham
D J
DJ
Watson
S R
SR
Doherty
P C
PC
D000818:Animals; D001853:Bone Marrow / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D007109:Immunity; D008221:Lymphoid Tissue / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009975:Orthomyxoviridae / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000276:immunology
D016201:Receptors, Lymphocyte Homing