Journal
JOURNAL OF IMMUNOLOGY
Volume 190, Issue 8, Pages 3985-3993Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1203213
Keywords
-
Categories
Funding
- Biotechnology and Biological Sciences Council, U.K.
- Agence Nationale de la Recherche, France [ANR-BBSRC-SysBio 07BSYS007]
- Biotechnology and Biological Sciences Research Council [BB/F005504/1] Funding Source: researchfish
- Medical Research Council [MC_U117573801, MC_PC_13055] Funding Source: researchfish
- BBSRC [BB/F005504/1] Funding Source: UKRI
- MRC [MC_U117573801, MC_PC_13055] Funding Source: UKRI
Ask authors/readers for more resources
Lymphopenia induces T cells to undergo cell divisions as part of a homeostatic response mechanism. The clonal response to lymphopenia is extremely diverse, and it is unknown whether this heterogeneity represents distinct mechanisms of cell-cycle control or whether a common mechanism can account for the diversity. We addressed this question by combining in vivo and mathematical modeling of lymphopenia-induced proliferation (LIP) of two distinct T cell clonotypes. OT-I T cells undergo rapid LIP accompanied by differentiation that superficially resembles Ag-induced proliferation, whereas F5 T cells divide slowly and remain naive. Both F5 and OT-I LIP responses were most accurately described by a single stochastic division model where the rate of cell division was exponentially decreased with increasing cell numbers. The model successfully identified key biological parameters of the response and accurately predicted the homeostatic set point of each clone. Significantly, the model was successful in predicting interclonal competition between OT-I and F5 T cells, consistent with competition for the same resource(s) required for homeostatic proliferation. Our results show that diverse and heterogenous clonal T cell responses can be accounted for by a single common model of homeostasis. The Journal of Immunology, 2013, 190: 3985-3993.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available