The Primary Responses of Murine Neonatal Lymph Node CD4<sup>+</sup> Cells are Th2‐skewed and are Sufficient for the Development of Th2‐biased Memory

Adkins, Becky; Bu, Yurong; Vincek, Vladimir; Guevara, Patricia

doi:10.1080/10446670310001598474

Cited by 29 publications

(18 citation statements)

References 29 publications

(39 reference statements)

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“…Given that we focused on juvenile 21-28-d-old mice, it is prudent to mention that it is known that neonate mice have an impaired development of Th function (46)(47)(48). For example, CD4 + cells isolated from neonatal murine lymph nodes have a Th2-skewed primary immune response that induces a Th2-biased memory response toward secondary insults (49). In contrast, 3-wk-old juvenile mice were used in this study in models of helminth infection, demonstrating decreased or delayed type 2 immune responses compared with adult animals.…”

Section: Discussionmentioning

confidence: 99%

Impaired Basophil Induction Leads to an Age-Dependent Innate Defect in Type 2 Immunity during Helminth Infection in Mice

Nel

Hams

Saunders

et al. 2011

The Journal of Immunology

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Parasitic-infection studies on rhesus macaque monkeys have shown juvenile animals to be more susceptible to infection than adults, but the immunological mechanism for this is not known. In this study, we investigated the age-dependent genesis of helminth-induced type 2 immune responses using adult (6–8-wk-old) and juvenile (21–28-d-old) mice. Following infection with the parasitic nematode Nippostrongylus brasiliensis, juvenile mice had increased susceptibility to infection relative to adult mice. Juvenile mice developed a delayed type 2 immune response with decreased Th2 cytokine production, IgE Ab responses, mouse mast cell protease 1 levels, and intestinal goblet cell induction. This innate immune defect in juvenile mice was independent of TLR signaling, dendritic cells, or CD4+ cell function. Using IL-4–eGFP mice, it was demonstrated that the numbers of IL-4–producing basophil and eosinophils were comparable in young and adult naive mice; however, following helminth infection, the early induction of these cells was impaired in juvenile mice relative to older animals. In nonhelminth models, there was an innate in vivo defect in activation of basophils, but not eosinophils, in juvenile mice compared with adult animals. The specific role for basophils in this innate defect in helminth-induced type 2 immunity was confirmed by the capacity of adoptively transferred adult-derived basophils, but not eosinophils, to restore the ability of juvenile mice to expel N. brasiliensis. The defect in juvenile mice with regard to helminth-induced innate basophil-mediated type 2 response is relevant to allergic conditions.

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Section: Discussionmentioning

confidence: 99%

Impaired Basophil Induction Leads to an Age-Dependent Innate Defect in Type 2 Immunity during Helminth Infection in Mice

Nel

Hams

Saunders

et al. 2011

The Journal of Immunology

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“…The understanding of the neonatal immune system is rudimentary at best, regardless of the species. In general, though, neonatal cell-mediated responses are thought to be Th2 biased (1,3,4). Given that rhodococcal pneumonia occurs when a Th2 immune response is induced, the Th2 bias of neonates is clearly a potential reason that foals are uniquely susceptible.…”

Section: Vol 73 2005 R Equi-specific Ctl 2089mentioning

confidence: 99%

Rhodococcus equi-Specific Cytotoxic T Lymphocytes in Immune Horses and Development in Asymptomatic Foals

Patton¹,

McGuire²,

Hines

et al. 2005

Infect Immun

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Rhodococcus equi is an important cause of pneumonia in young horses; however, adult horses are immune due to their ability to mount protective recall responses. In this study, the hypothesis that R. equi-specific cytotoxic T lymphocytes (CTL) are present in the lung of immune horses was tested. Bronchoalveolar lavage (BAL)-derived pulmonary T lymphocytes stimulated with R. equi lysed infected alveolar macrophages and peripheral blood adherent cells (PBAC). As with CTL obtained from the blood, killing of R. equi-infected targets by pulmonary effectors was not restricted by equine lymphocyte alloantigen-A (ELA-A; classical major histocompatibility complex class I), suggesting a novel or nonclassical method of antigen presentation. To determine whether or not CTL activity coincided with the age-associated susceptibility to rhodococcal pneumonia, CTL were evaluated in foals. R. equi-stimulated peripheral blood mononuclear cells (PBMC) from 3-week-old foals were unable to lyse either autologous perinatal or mismatched adult PBAC targets. The defect was not with the perinatal targets, as adult CTL effectors efficiently killed infected targets from 3-week-old foals. In contrast, significant CTL activity was present in three of five foals at 6 weeks of age, and significant specific lysis was induced by PBMC from all foals at 8 weeks of age. As with adults, lysis was ELA-A unrestricted. Two previously described monoclonal antibodies, BCD1b3 and CD1F2/1B12.1, were used to examine the expression of CD1, a nonclassical antigen-presenting molecule, on CTL targets. These antibodies cross-reacted with both foal and adult PBAC. However, neither antibody bound alveolar macrophages, suggesting that the R. equi-specific, major histocompatibility complex-unrestricted lysis is not restricted by a surface molecule identified by these antibodies.

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“…7 Just as both fetal and adult monocytes phosphorylate the canonical Fetal and neonatal immune responses have been previously described to preferentially activate Th2 responses rather than Th1, though most of the evidence for this skew has been shown mice. 41,42 Given that unexpected STAT phosphorylation responses were seen in response to a classical Th1 cytokine (IFN-g), we sought to determine whether fetal monocyte responses to a keystone Th2 cytokine (IL-4) were also different from responses described in adults. As in the case of IFN-g, stimulation with IL-4 prompted both fetal and adult monocytes to phosphorylate the canonical intermediate STAT6.…”

Section: Org Frommentioning

confidence: 99%

Distinct functional programming of human fetal and adult monocytes

Krow-Lucal¹,

Kim²,

Burt

et al. 2014

Blood

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Key Points• Human fetal and adult classical monocytes have distinct baseline transcriptional and signaling programs.• Transcriptional and signaling differences in fetal monocytes underlie stronger responses to cytokine stimulation.Preterm birth affects 1 out of 9 infants in the United States and is the leading cause of long-term neurologic handicap and infant mortality, accounting for 35% of all infant deaths in 2008. Although cytokines including interferon-g (IFN-g), interleukin-10 (IL-10), IL-6, and IL-1 are produced in response to in utero infection and are strongly associated with preterm labor, little is known about how human fetal immune cells respond to these cytokines. We demonstrate that fetal and adult CD14 1 CD16 2 classical monocytes are distinct in terms of basal transcriptional profiles and in phosphorylation of signal transducers and activators of transcription (STATs) in response to cytokines. Fetal monocytes phosphorylate canonical and noncanonical STATs and respond more strongly to IFN-g, IL-6, and IL-4 than adult monocytes. We demonstrate a higher ratio of SOCS3 to IL-6 receptor in adult monocytes than in fetal monocytes, potentially explaining differences in STAT phosphorylation. Additionally, IFN-g signaling results in upregulation of antigen presentation and costimulatory machinery in adult, but not fetal, monocytes. These findings represent the first evidence that primary human fetal and adult monocytes are functionally distinct, potentially explaining how these cells respond differentially to cytokines implicated in development, in utero infections, and the pathogenesis of preterm labor. (Blood.

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The Primary Responses of Murine Neonatal Lymph Node CD4⁺ Cells are Th2‐skewed and are Sufficient for the Development of Th2‐biased Memory

Cited by 29 publications

References 29 publications

Impaired Basophil Induction Leads to an Age-Dependent Innate Defect in Type 2 Immunity during Helminth Infection in Mice

Impaired Basophil Induction Leads to an Age-Dependent Innate Defect in Type 2 Immunity during Helminth Infection in Mice

Rhodococcus equi-Specific Cytotoxic T Lymphocytes in Immune Horses and Development in Asymptomatic Foals

Distinct functional programming of human fetal and adult monocytes

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The Primary Responses of Murine Neonatal Lymph Node CD4+ Cells are Th2‐skewed and are Sufficient for the Development of Th2‐biased Memory

Cited by 29 publications

References 29 publications

Impaired Basophil Induction Leads to an Age-Dependent Innate Defect in Type 2 Immunity during Helminth Infection in Mice

Impaired Basophil Induction Leads to an Age-Dependent Innate Defect in Type 2 Immunity during Helminth Infection in Mice

Rhodococcus equi-Specific Cytotoxic T Lymphocytes in Immune Horses and Development in Asymptomatic Foals

Distinct functional programming of human fetal and adult monocytes

Contact Info

Product

Resources

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The Primary Responses of Murine Neonatal Lymph Node CD4⁺ Cells are Th2‐skewed and are Sufficient for the Development of Th2‐biased Memory