Flexibility accompanies commitment of memory CD4 lymphocytes derived from IL-4 locus-activated precursors

Adeeku, Eric K.; Gudapati, Prathyusha; Mendez-Fernandez, Yanice; Kaer, Luc Van; Boothby, Mark

doi:10.1073/pnas.0704807105

Cited by 10 publications

(17 citation statements)

References 48 publications

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“…It has been demonstrated in vitro that the Th2 phenotype, once generated can persist stably and irreversibly by repression of IL-12 receptor signaling (39) and that a short duration of Th2 development can generate memory populations with high level Th2 cytokine production capabilities on recall activation (40). Persistence of Th2 memory with increased IL-4 responses on reinfection has been well demonstrated using IL-4 reporter mice infected with the gastrointestinal nematodes Heligmosomoides polygyrus (41) and Trichuris muris (42) even after clearance of parasite.…”

Section: Discussionmentioning

confidence: 99%

Filarial Infection Modulates the Immune Response to Mycobacterium tuberculosis through Expansion of CD4+ IL-4 Memory T Cells

Chatterjee

Clark

Lugli

et al. 2015

The Journal of Immunology

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Exaggerated CD4+T helper 2-specific cytokine producing memory T cell responses developing concomitantly with a T helper1 response might have a detrimental role in immunity to infection caused by Mycobacterium tuberculosis (Mtb). To assess the dynamics of antigen (Ag)-specific memory T cell compartments in the context of filarial infection we used multiparameter flow cytometry on PBMCs from 25 microfilaremic filarial -infected (Inf) and 14 filarial-uninfected (Uninf) subjects following stimulation with filarial (BmA) or with the Mycobacterium tuberculosis (Mtb)-specific Ag CFP10. Our data demonstrated that the Inf group not only had a marked increase in BmA-specific CD4+IL-4+ cells (Median net frequency compared to baseline (Fo)=0.09% vs. 0.01%, p=0.038) but also to CFP10 (Fo =0.16% vs. 0.007%, p=0.04) and Staphylococcal Enterotoxin B (SEB) (Fo =0.49% vs. 0.26%, p=0.04). The Inf subjects showed a BmA-specific expansion of CD4+CD45RO+IL-4+ producing central memory (TCM, CD45RO+CCR7+CD27+) (Fo =1.1% vs. 0.5%, p=0.04) as well as effector memory (TEM CD45RO+CCR7-CD27-) (Fo =1.5% vs. 0.2%, p=0.03) with a similar but non-significant response to CFP10. In addition, there was expansion of CD4+ IL-4+ CD45RA+ CCR7+CD27+ (naïve-like) in Inf individuals compared to Uninf subjects. Among Inf subjects with definitive latent tuberculosis , there were no differences in frequencies of IL-4 producing cells within any of the memory compartments compared to the Uninf group. Our data suggest that filarial infection induces antigen-specific, exaggerated IL-4 responses in distinct T cell memory compartments to Mtb-specific antigens, which are attenuated in subjects who are able to mount a delayed type hypersensitivity reaction to Mtb.

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Section: Discussionmentioning

confidence: 99%

Filarial Infection Modulates the Immune Response to Mycobacterium tuberculosis through Expansion of CD4+ IL-4 Memory T Cells

Chatterjee

Clark

Lugli

et al. 2015

The Journal of Immunology

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“…Th cells that secrete IFNγ, IL-4 or IL-17 can acquire attributes of T follicular helper cells [33–35]. Even Th2 memory cells are not entirely stable and are able to produce IFNγ after exposure to a new cytokine environment [36,37]. Together, these observations suggest that few Th cell subsets are completely fixed and with appropriate signals, cells may acquire new phenotypes.…”

Section: A Lineage a Transient Phenotype Or Just One Cytokine Of Manymentioning

confidence: 99%

Regulating Il9 transcription in T helper cells

Perumal¹,

Kaplan²

2011

Trends in Immunology

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T helper cells are critical for the development of immunity to infections and inflammatory disease. The acquisition of specific cytokine-secreting profiles, primed by the cytokine microenvironment, is required for effector function of Th cells. The most recent addition to the growing list of effector subsets are Th9 cells that secrete IL-9. In this article we propose a model for the transcriptional regulation of the Il9 gene in IL-9-expressing T cells and the relatedness of this subset to other Th phenotypes. We suggest that transcription factors restricted to certain Th subsets, and common among several subsets, may play a role in the plasticity of Th9 cells. Differentiation of Th subsetsThe effector function of T helper subsets relies upon the production of particular cytokines. The cytokine-secreting potential of effector T helper subsets requires the activation and expression of transcription factors that promote the development of each subset. Differentiation is stimulated by the cytokine microenvironment and the activation of Signal Transducer and Activator of Transcription (STAT) proteins that initiate specific genetic programs (Fig. 1A). The subset-specific genetic programs include transcription factors required for the expression of cytokines and other genes that contribute to the effector function of each subset (Fig. 1A). While a single transcription factor is often called a "master regulator", the appropriate development and function of Th subsets requires the coordinated activity of numerous transcription factors, some that are specific to a particular Th subset, and some that are shared among several subsets. The most recent addition to a growing continuum of Th subsets is the Th9 phenotype. These cells that develop in vitro in the presence of IL-4 and TGF-β, secrete high levels of IL-9, as well as IL-10, CCL17 and CCL22 [1][2][3][4]. However, the transcription factors regulating the hallmark cytokine IL-9 are not well defined. In this article we discuss factors that are specific to Th9 cells, or common among Th9 and other Th subsets, each of which may contribute to the expression of the Il9 gene and the plasticity of phenotype between Th9 and other Th subsets.

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“…There had been some evidence that cytokine producing cells in the primary response could not develop into memory cells [40], suggesting that vaccines should aim to generate T CM cells rather than T EM cells. However, two recent studies have convincingly shown that cells making IFNγ in the primary response can survive into the memory pool [102, 103] and cells that have activated their IL4 locus during priming can also become memory cells [104]. Therefore, it seems likely that vaccines should aim to induce T cells that can make the appropriate cytokine response for the infection they are designed to protect against.…”

Section: Can Cd4 Memory T Cells Provide Protective Responses?mentioning

confidence: 99%

CD4 memory T cells: What are they and what can they do?

MacLeod¹,

Clambey²,

Kappler³

et al. 2009

Seminars in Immunology

115

109

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Immunological memory provides the basis for successful vaccines. It is important to understand the properties of memory cells. There is much known about the phenotype and functions of memory CD8 T cells, less about memory B cells, while CD4 memory T cells have proved difficult to study. Differences in the types of memory CD4 cells studied and the difficulties of tracking the small number of cells has led to conflicting and unclear results. Here we discuss the different systems used to study CD4 memory cells and ask whether, and in what circumstances, memory CD4 cells could provide protection against infections.

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Flexibility accompanies commitment of memory CD4 lymphocytes derived from IL-4 locus-activated precursors

Cited by 10 publications

References 48 publications

Filarial Infection Modulates the Immune Response to Mycobacterium tuberculosis through Expansion of CD4+ IL-4 Memory T Cells

Filarial Infection Modulates the Immune Response to Mycobacterium tuberculosis through Expansion of CD4+ IL-4 Memory T Cells

Regulating Il9 transcription in T helper cells

CD4 memory T cells: What are they and what can they do?

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