Naturally activated CD4+ T cells are highly enriched for cytokine-producing cells

Cederbom, Lukas; Bandeira, António; Coutinho, António; Ivars, Fredrik

doi:10.1002/(sici)1521-4141(199806)28:06<1934::aid-immu1934>3.0.co;2-1

Cited by 8 publications

(4 citation statements)

References 35 publications

(23 reference statements)

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“…Further observations, which are presented in Table 1, show that the 'helper activity', required to support thymocyte responses, can be abrogated by the removal of CD44 hi cells, but not by the removal of cells bearing high levels of CD45RB or CD62L. This surface phenotype of CD44 hi , CD45RB low and CD62L low is the same as 'naturally'-activated CD4 + T cells found in normal mice (36,37). Collectively, these observations lead us to suggest that the syngeneic (radiation resistant) CD4 + T h , which are required for the generation of allo-specific thymocyte responses and are present in spleen, are activated T cells.…”

Section: Resultsmentioning

confidence: 70%

Activation of thymic T cells by MHC alloantigen requires syngeneic, activated CD4+ T cells and B cells as APC

Strutt¹,

Uzonna

McKinstry³

et al. 2006

International Immunology

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We examine here the in vitro requirements to activate immunocompetent T cells, present among thymocytes, to give rise to CTL, CD4+ T cells producing IL-2 and CD8+ T cells producing IFN-gamma. These thymocytes are naive in not having received antigen-dependent signals characteristic of the periphery. Their activation, upon stimulation with allogeneic spleen cells depleted of T cells, referred to here as allogeneic antigen-presenting cells (APCs), to produce allo-MHC-specific effector T cells, requires activated (radiation resistant) CD4+ T cells, syngeneic with the responding thymocytes. We refer here to these T cells as 'help'. Furthermore, optimal T cell activation requires an Ig+ B220+ cell in the allogeneic APC population, most probably a B cell. The allogeneic APCs cannot be replaced by conventional bone marrow (BM)-derived dendritic cells (DCs) activated by CD40 ligation or exposure to LPS. The requirements for both help and allogeneic B cells in the activation of thymocytes contrast with the requirements to generate substantial responses from splenic T cell populations. Activated, BM-derived DCs stimulate substantial splenic responses without help. These different requirements for activation could reflect the fact that thymocytes have not received an exit-thymus signal and/or that splenic T cells are heterogeneous, containing naive, memory and partially-activated T cells.

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Section: Resultsmentioning

confidence: 70%

Activation of thymic T cells by MHC alloantigen requires syngeneic, activated CD4+ T cells and B cells as APC

Strutt¹,

Uzonna

McKinstry³

et al. 2006

International Immunology

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“…Moreover, few IL-5-producing cells were detected in the culture of anti-CD3-stimulated CD4 ϩ CD25 ϩ T cells by intracellular cytokine analysis (data not shown). These observations suggest that the majority of CD4 ϩ CD25 ϩ T cells in nonimmunized DO10 mice differ from "naturally activated" CD4 ϩ T cells (24), because it has been shown that "naturally activated" CD4 ϩ T cells are large in size and rapidly produce a large amount of cytokines upon activation (24).…”

Section: Cd4 ϩ Cd25 ϩ T Cells In Nonimmunized Do10 Mice Differ From Nmentioning

confidence: 97%

Role of CD4⁺CD25⁺Regulatory T Cells in T Helper 2 Cell-mediated Allergic Inflammation in the Airways

Suto

Nakajima

Kagami

et al. 2001

Am J Respir Crit Care Med

111

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It has recently been shown that CD4(+) CD25(+) T cells are immunoregulatory T cells that prevent CD4(+) T cell-mediated organ-specific autoimmune diseases. To determine whether CD4(+) CD25(+) T cells downregulate Th2 cell-mediated allergic inflammation in the airways, we studied antigen-induced eosinophil recruitment in the airways in BALB/c Rag-2(-)(/-) mice transferred with CD4(+) CD25(+) T cell-depleted or unfractionated T cells from ovalbumin-specific TCR transgenic mice. Antigen-induced eosinophil recruitment into the airways was significantly decreased in the mice transferred with CD4(+) CD25(+) T cell-depleted splenocytes as compared with those transferred with unfractionated splenocytes. On the other hand, the depletion of CD4(+) CD25(+) T cells increased antigen-induced neutrophil and T cell recruitment in the airways of the mice. The depletion of CD4(+) CD25(+) T cells also decreased antigen-induced IL-4 and IL-5 production in the airways of the mice. Finally, the depletion of CD4(+) CD25(+) T cells prevented antigen-induced Th2 cell differentiation in vitro but increased the differentiation of Th1 cells. These results indicate that CD4(+) CD25(+) T cells modulate the Th1 and Th2 cell balance toward Th2 cells and thus upregulate Th2 cell-mediated allergic inflammation in the airways.

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“…Furthermore, the experiments also revealed that only ϳ6% of the cCD40L ϩ CD4 ϩ T cells were in the dividing phase (Table II). Previous studies have shown that the spleen contains a small number of naturally activated large T cells (30), which may contain preformed cCD40L. To study whether CD40L…”

Section: Cd4mentioning

confidence: 99%

CD4+ T Lymphocytes with Constitutive CD40 Ligand in Preautoimmune (NZB × NZW)F1 Lupus-Prone Mice: Phenotype and Possible Role in Autoreactivity

Lettesjö¹,

Burd²,

Mageed³

2000

The Journal of Immunology

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Lupus disease is marked by B lymphocyte hyperactivity and the production of Abs to dsDNA. The production of these anti-dsDNA Abs is T lymphocyte dependent. However, it is not clear how CD4+ T lymphocytes provide help for B lymphocytes to produce IgG anti-dsDNA Abs. One possible mechanism is suggested by studies showing that human patients with systemic lupus erythematosus and lupus mice have increased numbers of CD40 ligand (CD40L)+ T and B lymphocytes. The results described in this study reveal that young, clinically healthy lupus-prone New Zealand Black × New Zealand White F1 (BWF1) mice have naive CD4+ T cells with preformed CD40L. These cells contribute to a brisk response to immunization and to the production of anti-dsDNA Abs. In vitro experiments revealed that CD4+ T cells with preformed CD40L could, upon stimulation, provide antiapoptotic signals for B cells but could not induce proliferation or reduce activation threshold. These results suggest that the direct target cells for the effect of T cells with preformed CD40L in lupus may not be B lymphocytes.

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Naturally activated CD4+ T cells are highly enriched for cytokine-producing cells

Cited by 8 publications

References 35 publications

Activation of thymic T cells by MHC alloantigen requires syngeneic, activated CD4+ T cells and B cells as APC

Activation of thymic T cells by MHC alloantigen requires syngeneic, activated CD4+ T cells and B cells as APC

Role of CD4⁺CD25⁺Regulatory T Cells in T Helper 2 Cell-mediated Allergic Inflammation in the Airways

CD4+ T Lymphocytes with Constitutive CD40 Ligand in Preautoimmune (NZB × NZW)F1 Lupus-Prone Mice: Phenotype and Possible Role in Autoreactivity

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Naturally activated CD4+ T cells are highly enriched for cytokine-producing cells

Cited by 8 publications

References 35 publications

Activation of thymic T cells by MHC alloantigen requires syngeneic, activated CD4+ T cells and B cells as APC

Activation of thymic T cells by MHC alloantigen requires syngeneic, activated CD4+ T cells and B cells as APC

Role of CD4+CD25+Regulatory T Cells in T Helper 2 Cell-mediated Allergic Inflammation in the Airways

CD4+ T Lymphocytes with Constitutive CD40 Ligand in Preautoimmune (NZB × NZW)F1 Lupus-Prone Mice: Phenotype and Possible Role in Autoreactivity

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Role of CD4⁺CD25⁺Regulatory T Cells in T Helper 2 Cell-mediated Allergic Inflammation in the Airways