Quantitative analysis of T cell homeostatic proliferation.
T cell homeostatic proliferation occurs on transfer of T cells into lymphopenic recipients; transferred cells undergo several rounds of division in the absence of specific antigen stimulation. For a quantitative analysis of this phenomenon, we applied a mathematical method to describe proliferating T cells to match peak distributions from actual CFSE dilution data. For in vitro stimulation of T cells with anti-CD3/anti-CD28, our simulation confirmed a high proportion of cells entering cell cycle with a low proportion undergoing apoptosis. When applied to homeostatic proliferation, it described striking differences in CD4 and CD8 T cell proliferation rates, and accurately predicted that successive divisions were accompanied by higher rates of apoptosis, limiting the accumulation of proliferating cells. Thus, the presence of multiple CFSE dilution peaks cannot be considered equivalent to lymphocyte expansion. Finally, genetic effects were identified that may help explain links between homeostatic proliferation and autoimmunity.
Li
Cheng-Rui
CR
Division of Biomedical Sciences, University of California Riverside, 900 University Avenue, Riverside, CA 92521, USA.
Santoso
Sharon
S
Lo
David D
DD
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002452:Cell Count; D049109:Cell Proliferation; D002478:Cells, Cultured; D005434:Flow Cytometry; D006706:Homeostasis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018448:Models, Immunological