Ligation of CD2 Provides a Strong Helper Signal for the Production of the Type 2 Cytokines Interleukin-4 and -5 by Memory T Cells

Peng, Xiaohui; Kasran, Ahmad; Bullens, Dominique; Ceuppens, Jan L.

doi:10.1006/cimm.1997.1197

Cited by 13 publications

(8 citation statements)

References 47 publications

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“…These findings are consistent with previous reports that ligation of CD2 by CD48 augments antigen-driven proliferation and IL-2 production by CD4 1 T cells, (15) whereas T cells from CD2 2/2 mice exhibit diminished IFN-g production and proliferation following antigen-triggered stimulation. (40) Impaired IL-2 and IFN-g production in the presence of anti-CD2 mAb was not due to enhanced production of type 2 cytokines in response to CD2 ligation, as has been reported in some experimental systems, (32,33) as IL-10 synthesis by anti-CD3-activated T cells was also inhibited in the presence of anti-CD2 mAb. Moreover, anti-CD48 mAb had a similar inhibitory effect on IL-10 production.…”

Section: Discussionsupporting

confidence: 59%

“…CD2 ligation by specific mAb has been reported to induce type 2 cytokine synthesis by T cells in some experimental systems, (32,33) which might account for the observed reduction in type 1 cytokine production and impaired CTL induction in the presence of anti-CD2 mAb. However, ELISA measurements of IL-10 levels in culture supernatants of T cells activated in the presence of anti-CD2 mAb revealed a dramatic reduction in IL-10 synthesis in comparison to control culture supernatants (211 6 8 pg/ml vs. 516 6 28 pg/ml, p , 0.001).…”

Section: Cd2-cd8 Interactions Are Required For Il-2 and Ifng Productimentioning

confidence: 99%

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CD2-CD48 Interactions Promote Cytotoxic T Lymphocyte Induction and Function: Anti-CD2 and Anti-CD48 Antibodies Impair Cytokine Synthesis, Proliferation, Target Recognition/Adhesion, and Cytotoxicity

Musgrave

Watson²

2003

Journal of Interferon & Cytokine Research

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The role of CD2 signaling in cytotoxic T lymphocyte (CTL) development was examined by stimulating mouse T cells with anti-CD3 monoclonal antibody (mAb) in the absence or presence of anti-CD2 mAb or anti-CD48 mAb or both. Induction of nonspecific CTL and interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) synthesis were impaired in the absence of CD2-CD48 interactions. Anti-CD2 mAb also inhibited activation-induced expression of the high-affinity IL-2 receptor (IL-2R). In contrast, IFN-gamma receptor (IFNGR) expression was increased in the presence of anti-CD2 mAb. Reduced cytotoxicity by CTL induced in the absence of CD2-CD48 interactions was associated with a diminished ability of CTL to conjugate with target cells and reduced expression of granzyme B and perforin. Anti-CD2 mAb did not affect expression of Fas ligand and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) by anti-CD3-activated T cells. Cytotoxic effector function and granzyme B and perforin expression were rescued when exogenous IL-2 and IFN-gamma were added in combination with anti-CD2 mAb to anti-CD3-activated T cells at initiation of culture. We conclude that CD2-CD48 interactions during T cell activation are critical for the synthesis of sufficient IL-2 and IFN-gamma to drive CD8(+) T cells to differentiate into functional cytotoxic effector cells.

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Section: Discussionsupporting

confidence: 59%

Section: Cd2-cd8 Interactions Are Required For Il-2 and Ifng Productimentioning

confidence: 99%

CD2-CD48 Interactions Promote Cytotoxic T Lymphocyte Induction and Function: Anti-CD2 and Anti-CD48 Antibodies Impair Cytokine Synthesis, Proliferation, Target Recognition/Adhesion, and Cytotoxicity

Musgrave

Watson²

2003

Journal of Interferon & Cytokine Research

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“…Our results clearly show that IL-4 production can be induced in cultures of freshly isolated T cells when the IL-4Ra chain has been blocked. Since IL-4 production in these cultures is restricted to memory cells [28], we can conclude that at least human memory and/or effector T cells can produce IL-4 without IL-4 signalling. We can, however, not rule out that T cells may rely on IL-4-IL-4R interaction for IL-4 up-regulation.…”

Section: Discussionmentioning

confidence: 83%

Effects of anti-IL-4 receptor monoclonal antibody onin vitroT cell cytokine levels: IL-4 production by T cells from non-atopic donors

Bullens

Kasran

Peng

et al. 1998

Clinical and Experimental Immunology

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IL-4 is a pleiotropic cytokine which is involved in the development of atopic diseases. Only limited data exist on IL-4 production in humans, and the relative contribution to atopy of either unbalanced IL-4 production, or increased IL-4-responsiveness of target cells, is still unknown. The use of a MoAb to the IL-4 receptor alpha-chain (IL-4Ralpha) enabled us to demonstrate that IL-4 production in vitro is usually underestimated, due to in vitro consumption, even in cultures of purified T cells. When IL-4 consumption was blocked, it became evident that CD80 and CD86 both provide effective costimulatory signals for high IL-4 production. Moreover, we found that even stimulation with a soluble antigen (tetanus toxoid) induces IL-4 production by T cells from healthy non-atopic donors. Both sets of data imply that IL-4 is not required for IL-4 production by memory and/or effector T cells. Our data further show that endogenous IL-4 activity modulates IL-10 and interferon-gamma production by T cells in opposite directions. The use of this receptor-blocking antibody will thus be helpful for in vitro studies on IL-4 regulation. Consumption of IL-4 by different cell types during in vitro cultures might have interfered with previous attempts to quantify IL-4 production by human T cells.

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“…18,19 MAb directed at CD2 inhibit T-cell proliferation, 20,21 induce LPL-T apoptosis, 16 inhibit Th 1 cytokine production, and induce Th 2 and Th 3 cytokines. [22][23][24] Accordingly, aCD2 mAb were used successfully in both transplantation models, [25][26][27][28] arthritis and multiple sclerosis animal models. [29][30][31] Clinical studies suggest that CD2 is a promising target in psoriasis.…”

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confidence: 99%

αCD2 mAb treatment safely attenuates adoptive transfer colitis

Pawlowski

Kakirman

Kühl

et al. 2005

Laboratory Investigation

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Increased proliferation, defective apoptosis, and cytokine dysregulation of T lymphocytes are thought to be important for the pathogenesis of inflammatory bowel disease. Since these phenomena can be corrected by aCD2 mAb, we asked whether CD2 directed immunotherapy safely prevents and/or ameliorates adoptive transfer colitis. Colitis was induced by transfer of CD4 þ T cell blasts to syngenic RAG1 À/À mice or CD45RB high CD4 þ T cells to SCID mice. The aCD2 mAb 12-15 or rat IgG was given, starting either initially or upon first signs of colitis. Disease activity was assessed by clinical monitoring, microscopic scoring, hemoccult, endoscopy, and blood count analysis. Cytokine production of stimulated LPL was measured by ELISA and cell proliferation by [ 3 H]-thymidine incorporation. Parasite control was analyzed in a murine model of infection with Toxoplasma gondii. The aCD2 mAb significantly increased mean survival time when starting at transfer of blasts (survival 435 days: aCD2 69% vs 0% of controls, Po0.001). In the SCID colitis model hematochezia and macroscopic colitis were delayed. When used in established T-cell blast colitis, the benefit was less pronounced, even in combination with dexamethasone (mean survival7s.e.m.: aCD2 þ dexa: 13.572.9 vs dexa þ IgG: 6.371.0, Po0.05). In the preventive experiment the aCD2 mAb markedly reduced IL-2 secretion and T-cell proliferation. The immune response towards Toxoplasma gondii was not impaired. These studies show for the first time that CD2 directed immunotherapy can attenuate or delay adoptive transfer colitis and ameliorate established colitis. Most likely inhibition of IL-2 secretion and T-cell proliferation are responsible for these effects. Still, immune defence towards T. gondii is maintained.

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Ligation of CD2 Provides a Strong Helper Signal for the Production of the Type 2 Cytokines Interleukin-4 and -5 by Memory T Cells

Cited by 13 publications

References 47 publications

CD2-CD48 Interactions Promote Cytotoxic T Lymphocyte Induction and Function: Anti-CD2 and Anti-CD48 Antibodies Impair Cytokine Synthesis, Proliferation, Target Recognition/Adhesion, and Cytotoxicity

CD2-CD48 Interactions Promote Cytotoxic T Lymphocyte Induction and Function: Anti-CD2 and Anti-CD48 Antibodies Impair Cytokine Synthesis, Proliferation, Target Recognition/Adhesion, and Cytotoxicity

Effects of anti-IL-4 receptor monoclonal antibody onin vitroT cell cytokine levels: IL-4 production by T cells from non-atopic donors

αCD2 mAb treatment safely attenuates adoptive transfer colitis

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