Selective depletion of eosinophils or neutrophils in mice impacts the efficiency of apoptotic cell clearance in the thymus.
Developing thymocytes undergo a rigorous selection process to ensure that the mature T cell population expresses a T cell receptor (TCR) repertoire that can functionally interact with major histocompatibility complexes (MHC). Over 90% of thymocytes fail this selection process and die. A small number of macrophages within the thymus are responsible for clearing the large number of dying thymocytes that must be continuously cleared. We studied the capacity of thymic macrophages to clear apoptotic cells under acute circumstances. This was done by synchronously inducing cell death in the thymus and then monitoring the clearance of apoptotic thymocytes. Interestingly, acute cell death was shown to recruit large numbers of CD11b(+) cells into the thymus. In the absence of a minor CSF-1 dependent population of macrophages, the recruitment of these CD11b(+) cells into the thymus was greatly reduced and the clearance of apoptotic cells was disrupted. To assess a possible role for the CD11b(+) cells in the clearance of apoptotic cells, we analyzed mice deficient for eosinophils and mice with defective trafficking of neutrophils. Failure to attract either eosinophils or neutrophils to the thymus resulted in the impaired clearance of apoptotic cells. These results suggested that there is crosstalk between cells of the innate immune system that is necessary for maximizing the efficiency of apoptotic cell removal.
Kim
Hye-Jung
HJ
Immunology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
Alonzo
Eric S
ES
Dorothee
Guillaume
G
Pollard
Jeffrey W
JW
Sant'Angelo
Derek B
DB
D000818:Animals; D017209:Apoptosis / Q000276:immunology / Q000528:radiation effects*; D039481:CD11b Antigen / Q000378:metabolism; D002478:Cells, Cultured; D004804:Eosinophils / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005720:Gamma Rays; D007113:Immunity, Innate / Q000502:physiology*; D007150:Immunohistochemistry; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism / Q000382:microbiology / Q000528:radiation effects; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects
D039481:CD11b Antigen