Critical Role of Interleukin 4 in the Induction of Neonatal Transplantation Tolerance

Donckier, Vincent; Wissing, Martin; Bruyns, Catherine; Abramowicz, Daniel; Lybin, M; Vanderhaeghen, Marie-Line; Goldman, Michel

doi:10.1097/00007890-199506000-00012

Cited by 76 publications

(35 citation statements)

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“…(Schurmans et al, 1990;Donckier et al, 1995;Gao et al, 1996). Together with our splenectomy experiments, this would suggest that Th2 dominance must be established during primary responses in the lymph nodes.…”

Section: Neonatal Lymph Nodes Are Sufficient To Generate and Maintainsupporting

confidence: 61%

“…Studies from the laboratory of M. Goldman (Donckier et al, 1995) showed that IL-4 RNA is upregulated in neonatal lymph nodes as early as 2 days after the injection of allogeneic cells. Our results, examining the responses of lymph node cells one week after the injection of allogeneic cells, confirm this result and extend it in two ways.…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that IL-4 production in vivo is necessary for the induction and maintenance of neonatally induced tolerance to semiallogeneic F1 cells (Schurmans et al, 1990;Donckier et al, 1995;Gao et al, 1996). Thus, we next tested whether the splenic Th2 dominant responses are required for the induction of tolerance to alloantigens.…”

Section: Neonatal Lymph Nodes Are Sufficient To Generate and Maintainmentioning

confidence: 98%

“…or i.v. with allogeneic cells subsequently reject, in a Th2-dependent manner, donor origin skin grafts transplanted to the tail in later adult life (Goldman et al, 1989;Schurmans et al, 1990;Chen et al, 1995;Donckier et al, 1995;Gao et al, 1996). How these Th2 dominant responses originally arise is, at present, unclear.…”

Section: Cd4mentioning

confidence: 99%

“…In normal neonates, Th2 responses have been shown to dominate in this transplantation model (Goldman et al, 1989;Schurmans et al, 1990;Chen et al, 1995;Donckier et al, 1995;Gao et al, 1996). To determine whether exclusive Th2 responses also developed in the absence of the spleen, the Th1/Th2 recall responses of lymph node cells from the same animals were monitored in vitro 49 days after the initial skin grafting.…”

Section: Neonatal Lymph Nodes Are Sufficient To Generate and Maintainmentioning

confidence: 99%

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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

Adkins

Vincek

et al. 2003

Journal of Immunology Research

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Exposure of neonatal mice to antigen often results in Th2-biased responses in later life. Examples of this Th2 tendency are (a) secondary antibody responses dominated by the Th2-associated IgG1 isotype and (b) Th2-mediated tolerance to alloantigens. We previously reported that neonates develop primary Th1 and Th2 function in the lymph nodes but exclusive Th2 primary splenic responses. Here, we have tested whether the Th2 bias of adults initially immunized as neonates is due to the early, primary Th2 polarization in the spleen. Surprisingly, removal of the spleen at birth had no affect on either IgG1-dominant secondary responses or the development of tolerance to alloantigens. Thus, neonatal lymph nodes are sufficient to generate Th2-biased function following neonatal antigen exposure. To understand how this could arise, we examined the primary Th1/Th2 responses of CD4 þ lymph node cells. Unlike the balanced Th1/Th2 responses seen with total lymph node cells, the primary responses of isolated CD4 þ cells were skewed to IL-4 producing function. These results suggest that the early development of Th2-dominant responses by lymph node CD4 þ cells contributes substantially to the subsequent development of Th2-dominant memory in neonates.

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Section: Neonatal Lymph Nodes Are Sufficient To Generate and Maintainsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Neonatal Lymph Nodes Are Sufficient To Generate and Maintainmentioning

confidence: 98%

Section: Cd4mentioning

confidence: 99%

Section: Neonatal Lymph Nodes Are Sufficient To Generate and Maintainmentioning

confidence: 99%

See 3 more Smart Citations

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

Adkins

Vincek

et al. 2003

Journal of Immunology Research

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IL-12 prevents neonatal induction of transplantation tolerance in mice

et al. 1998

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We investigated the effect of IL-12 on the induction of transplantation tolerance by neonatal injection of allogenic cells. We first observed that injection of newborn BALB/c mice with IL-12 and (A/J × BALB/c)F1 spleen cells prevented the Th2 alloimmune response induced by neonatal inoculation of F1 cells alone and allowed the differentiation of T cells secreting high amounts of IL-2 and IFN-+ in mixed lymphocyte cultures with donor-type stimulators. Furthermore , IL-12 administration resulted in the emergence of anti-donor cytotoxic T lympho-cyte responses although at lower levels than in control uninjected mice. In parallel, we found that mice injected at birth with IL-12 and F1 cells did not develop chimerism and were able to reject a donor-type skin graft as efficiently as control mice. We conclude that IL-12 inhibits the Th2 polarization of the newborn response to alloantigens and prevents thereby the establishment of transplantation tolerance.

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Hypereosinophilic syndrome induced by neonatal immunization against MHC class II alloantigen: critical role of IL-4

et al. 2002

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A significant proportion of patients with the hypereosinophilic syndrome suffer from oligoclonal expansion of type 2 helper T lymphocytes (Th2). Herein, we first provide evidence that mice immunized at birth against a single MHC class II alloantigen develop pathological features mimicking this variant of the hypereosinophilic syndrome. Indeed, C57BL / 6 mice injected at birth with (C57BL/ 6 × bm12)F1 spleen cells displayed T lymphocytes producing high levels of IL‐5 and IL‐13, increased blood eosinophil counts, eosinophilic infiltrates in various tissues, hyperplasia of lymphoid tissues, as well as serum hyperIgE. Moreover, eotaxin mRNA accumulated in the spleen of these animals. IL‐4‐deficient mice developed neither expansion of Th2 cells nor pathological changes except splenomegaly. Eotaxin mRNA accumulation was also prevented in these animals. We conclude that neonatal exposure to a single MHC class II alloantigen is sufficient to elicit an IL‐4‐dependent hypereosinophilic syndrome mimicking the lymphocytic variant of this disorder in humans.

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Critical Role of Interleukin 4 in the Induction of Neonatal Transplantation Tolerance

Cited by 76 publications

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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

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

IL-12 prevents neonatal induction of transplantation tolerance in mice

Hypereosinophilic syndrome induced by neonatal immunization against MHC class II alloantigen: critical role of IL-4

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Critical Role of Interleukin 4 in the Induction of Neonatal Transplantation Tolerance

Cited by 76 publications

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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

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

IL-12 prevents neonatal induction of transplantation tolerance in mice

Hypereosinophilic syndrome induced by neonatal immunization against MHC class II alloantigen: critical role of IL-4

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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

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