Identification of a branching process model for adaptive immune response

T-cell primary activation is a key event in the initiation of the adaptive immune response. Quantifying T-cell proliferation is extremely important to understand essential features of the immune response to vaccine or infection stimulus. Although mathematical models represent an attractive tool for analysis, they have been used almost exclusively for studying in vitro experiments. In this paper, we adopt a multi-type branching process with immigration to model T-cell proliferation in in vivo experiments. A maximum likelihood approach has been used to estimate model parameters, using T-cell relative frequencies instead of cell counts. Parameter estimates which represent the probabilities of division and death of the different cell generations, provide meaningful information on T-cell population kinetics.

[1]  Donata Medaglini,et al.  Distribution of Primed T Cells and Antigen-Loaded Antigen Presenting Cells Following Intranasal Immunization in Mice , 2011, PloS one.

[2]  Cliburn Chan,et al.  Reconstruction of cell population dynamics using CFSE , 2007, BMC Bioinformatics.

[3]  Linda Mark,et al.  Follicular helper T cells as cognate regulators of B cell immunity. , 2009, Current opinion in immunology.

[4]  Ollivier Hyrien,et al.  An age-dependent branching process model for the analysis of CFSE-labeling experiments , 2010, Biology Direct.

[5]  Donata Medaglini,et al.  In Vivo Activation of Naive CD4+ T Cells in Nasal Mucosa-Associated Lymphoid Tissue following Intranasal Immunization with Recombinant Streptococcus gordonii , 2006, Infection and Immunity.

[6]  Donata Medaglini,et al.  Primary Activation of Antigen-Specific Naive CD4+ and CD8+ T Cells following Intranasal Vaccination with Recombinant Bacteria , 2008, Infection and Immunity.

[7]  T. E. Harris,et al.  The Theory of Branching Processes. , 1963 .

[8]  Hulin Wu,et al.  Evaluation of Multitype Mathematical Models for CFSE-Labeling Experiment Data , 2012, Bulletin of mathematical biology.

[9]  P. Hodgkin,et al.  Intracellular competition for fates in the immune system. , 2012, Trends in cell biology.

[10]  A. Khoruts,et al.  Use of adoptive transfer of T‐cell antigen‐receptor‐transgenic T cells for the study of T‐cell activation in vivo , 1997, Immunological reviews.

[11]  Alan S. Perelson,et al.  Estimating Lymphocyte Division and Death Rates from CFSE Data , 2006, Bulletin of mathematical biology.

[12]  Donata Medaglini,et al.  Intranasal immunization with vaccine vector Streptococcus gordonii elicits primed CD4+ and CD8+ T cells in the genital and intestinal tracts. , 2010, Vaccine.

[13]  Volker Brauer,et al.  Adjuvanted H5N1 vaccine induces early CD4+ T cell response that predicts long-term persistence of protective antibody levels , 2009, Proceedings of the National Academy of Sciences.

[14]  P. Hodgkin,et al.  A model of immune regulation as a consequence of randomized lymphocyte division and death times , 2007, Proceedings of the National Academy of Sciences.

[15]  Alan S Perelson,et al.  Quantifying T lymphocyte turnover. , 2013, Journal of theoretical biology.

[16]  Nikolay M. Yanev,et al.  Relative frequencies in multitype branching processes , 2009, 0902.4773.

[17]  M. Quine,et al.  THE MULTI-TYPE GALTON-WATSON PROCESS WITH IMMIGRATION , 1970 .

[18]  Donata Medaglini,et al.  Adoptive transfer of transgenic T cells to study mucosal adjuvants. , 2009, Methods.