Massive and destructive T cell response to homeostatic cue in CD24-deficient lymphopenic hosts.
In response to a lymphopenic cue, T lymphocytes undergo a slow-paced homeostatic proliferation in an attempt to restore T cell cellularity. The molecular interaction that maintains the pace of homeostatic proliferation is unknown. In this study, we report that in lymphopenic CD24-deficient mice, T cells launch a massive proliferation that results in the rapid death of the recipient mice. The dividing T cells have phenotypes similar to those activated by cognate antigens. The rapid homeostatic proliferation is caused by a lack of CD24 on dendritic cells (DCs). Interestingly, although CD24 expression in T cells is required for optimal homeostatic proliferation in the wild-type (WT) host, mice lacking CD24 on all cell types still mount higher homeostatic proliferation than the WT mice. Thus, a lack of CD24 in the non-T host cells bypassed the requirement for T cell expression of CD24 in homeostatic proliferation in the WT host. Our data demonstrate that CD24 expressed on the DCs limits T cell response to homeostatic cue and prevents fatal damage associated with uncontrolled homeostatic proliferation.
Li
Ou
O
Division of Cancer Immunology, Department of Pathology, The Ohio State University Medical Center, Columbus, OH 43210, USA.
Chang
Xing
X
Zhang
Huiming
H
Kocak
Ergun
E
Ding
Cheng
C
Zheng
Pan
P
Liu
Yang
Y
D000818:Animals; D051927:CD24 Antigen / Q000235:genetics*; D049109:Cell Proliferation; D002478:Cells, Cultured; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D008212:Lymphocyte Depletion; D008231:Lymphopenia / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000473:pathology* / Q000637:transplantation
D051927:CD24 Antigen