%A Magombedze,Gesham %A Reddy,Pradeep %A Eda,Shigetoshi %A Ganusov,Vitaly %D 2013 %J Frontiers in Physiology %C %F %G English %K CD4+ T cells,differentiation,plasticity,mathematical modeling,johnes disease %Q %R 10.3389/fphys.2013.00206 %W %L %M %P %7 %8 2013-August-16 %9 Review %+ Prof Vitaly Ganusov,University of Tennessee,Department of Microbiology,1414 Cumberland Ave,Knoxville,37996,TN,United States,vitaly.ganusov@gmail.com %# %! CD4 T cell differentiation %* %< %T Cellular and population plasticity of helper CD4+ T cell responses %U https://www.frontiersin.org/articles/10.3389/fphys.2013.00206 %V 4 %0 JOURNAL ARTICLE %@ 1664-042X %X Vertebrates are constantly exposed to pathogens, and the adaptive immunity has most likely evolved to control and clear such infectious agents. CD4+ T cells are the major players in the adaptive immune response to pathogens. Following recognition of pathogen-derived antigens naïve CD4+ T cells differentiate into effectors which then control pathogen replication either directly by killing pathogen-infected cells or by assisting with generation of cytotoxic T lymphocytes (CTLs) or pathogen-specific antibodies. Pathogen-specific effector CD4+ T cells are highly heterogeneous in terms of cytokines they produce. Three major subtypes of effector CD4+ T cells have been identified: T-helper 1 (Th1) cells producing IFN-γ and TNF-α, Th2 cells producing IL-4 and IL-10, and Th17 cells producing IL-17. How this heterogeneity is maintained and what regulates changes in effector T cell composition during chronic infections remains poorly understood. In this review we discuss recent advances in our understanding of CD4+ T cell differentiation in response to microbial infections. We propose that a change in the phenotype of pathogen-specific effector CD4+ T cells during chronic infections, for example, from Th1 to Th2 response as observed in Mycobactrium avium ssp. paratuberculosis (MAP) infection of ruminants, can be achieved by conversion of T cells from one effector subset to another (cellular plasticity) or due to differences in kinetics (differentiation, proliferation, death) of different effector T cell subsets (population plasticity). We also shortly review mathematical models aimed at describing CD4+ T cell differentiation and outline areas for future experimental and theoretical research.