Chapter 12 : The Th1/Th2 Paradigm in Infections

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The extent of the diversity of T-cell responses is much larger than the original Th1/Th2 dichotomy, raising questions about the significance of the original sharply defined Th1 and Th2 phenotypes, the extent of diversity of T-cell cytokine patterns, the information used by the immune system to decide which type of response to induce, the signals that induce differentiation into these and other phenotypes in vivo, and the extent to which differentiation and continued differentiation occur during normal responses. The study of functional heterogeneity within the CD4 T-cell population with regard to infectious disease was prompted by studies in the early 1970s on the development of humoral and cell-mediated immunity to pathogens and experimental antigens. In addition, IFN-γ stimulates the production of immunoglobulin G antibodies, which mediate opsonization and phagocytosis of particulate organisms. Th1 responses are also associated with viral infections; a direct role for CD4 cells in viral clearance has not been demonstrated for most viruses, but Th1 responses may support the expansion of CD8 antiviral effectors. The authors expect that T cells expressing non- Th1, non-Th2 patterns may be essential for other diseases and that the crucial differences between the immune responses may be subtle. The requirement for multiple effector phenotypes is almost certainly due to the intensive interplay between the host response and each pathogen, driving the evolution of complex host defense strategies and equally complex evasion and interference tactics by the pathogen.

Citation: Mosmann T, Fowell D. 2002. The Th1/Th2 Paradigm in Infections, p 163-174. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch12
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Figure 1

Two models for the early differentiation of T cells. Black and gray triangles indicate expression of the cytokine genes of the Th2 and Th1 patterns, respectively. (A) In the stochastic model, the initial differentiation event results in a variety of progeny cells expressing random cytokine patterns, and only those cells expressing the mature Th2 phenotype are selected for further proliferation. (B) In the stochastic but directed model, the initial differentiation event results in the same random mixture of patterns, but then each cell continues to differentiate, in response to environmental cues, towards the final Th2 pattern.

Citation: Mosmann T, Fowell D. 2002. The Th1/Th2 Paradigm in Infections, p 163-174. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch12
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