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Michael Brandeau Lawrence, Brian J Schmidt, Arvind K Chavali, Lydia Glaw, Agent based model of the TH1/TH2 differentiation decision (51.3), The Journal of Immunology, Volume 178, Issue 1_Supplement, April 2007, Pages S96–S97, https://doi.org/10.4049/jimmunol.178.Supp.51.3
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Abstract
Adaptive immune responses tend to polarize to predominantly TH1 or TH2-directed, and this decision is critical for the clinical outcome of many diseases. For example, Leishmania species that elicit a TH2 response, such as donavani, can lead to visceral leishmaniasis, which is fatal if not treated. In contrast, the body is able to combat leishmaniasis and recover from species that tend to elicit a TH1 response, such as L. major. The type of response the immune system mounts is governed by a multifactorial process involving the nature of the antigen and co-stimulatory molecules expressed on antigen presenting cells (APCs). We developed an agent-based computational model using knowledge of immunological interactions recently elucidated by in vivo two-photon microscopy studies to investigate whether APCs could be engineered to elicit a TH1 response after a TH2 response was previously established by a pathogen. The model supports the stochastic repertoire scanning model and further suggests that this mechanism may help T-cells coordinate their response by sampling the cytokine cues left by other differentiating T-cells. Additional cell types, such as natural killer and memory cells, may be important for establishing the dynamics of the response and the ratio of TH1 to TH2 cells. Our model additionally suggests that engineered APCs have the potential to be a viable treatment method for diseases such as visceral leishmaniasis.
Supported by NIH R01 HL54614.
