PubMed Health⌕ Search

Biomedical subjects

A Cavani

Publications and source records attributed to A Cavani.

At least 19 recordsLinked to original sources
PubMed2005

Leukocyte extravasation as a target for anti-inflammatory therapy - Which molecule to choose?

In view of the central pathogenic importance of leukocyte extravasation in inflammatory skin diseases, therapeutic interference with this - surprisingly complex - process is clearly a promising new approach for treating these dermatoses. Despite some disappointments during the clinical use of these agents and despite their crippling price tag, the recent incorporation of biologicals that target defined molecular controls of leukocyte extravasation into dermatological and rheumatological practise, consequently, has greatly enriched our therapeutic options for battling major, chronic, inflammatory dermatoses such as psoriasis. However, the - as yet unresolved and still rather controversially discussed - critical question is: Which of the multiple steps that control leukocyte extravasation in the human system really offer the most promising, most pragmatic, and safest molecular targets for therapeutic intervention for which disease entity? The current debate intends to stimulate public and rational debate of this crucial issue, beyond the evident commercial interests that are touched by whatever stand one takes.

Anti-Inflammatory Agents↗
PubMed2001

Extracellular ATP induces a distorted maturation of dendritic cells and inhibits their capacity to initiate Th1 responses.

Dendritic cells (DCs) express functional purinergic receptors, but the effects of purine nucleotides on DC functions have been marginally investigated. In this study, we report on the ability of micromolar concentrations of ATP to affect the maturation and Ag-presenting function of monocyte-derived DCs in vitro. Chronic stimulation (24 h) of DCs with low, noncytotoxic ATP doses increased membrane expression of CD54, CD80, CD86, and CD83, slightly reduced the endocytic activity of DCs, and augmented their capacity to promote proliferation of allogeneic naive T lymphocytes. Moreover, ATP enhanced LPS- and soluble CD40 ligand-induced CD54, CD86, and CD83 expression. On the other hand, ATP markedly and dose-dependently inhibited LPS- and soluble CD40 ligand-dependent production of IL-1alpha, IL-1beta, TNF-alpha, IL-6, and IL-12, whereas IL-1 receptor antagonist and IL-10 production was not affected. As a result, T cell lines generated from allogeneic naive CD45RA(+) T cells primed with DCs matured in the presence of ATP produced lower amounts of IFN-gamma and higher levels of IL-4, IL-5, and IL-10 compared with T cell lines obtained with LPS-stimulated DCs. ATP inhibition of TNF-alpha and IL-12 production by mature DCs was not mediated by PGs or elevation of intracellular cAMP and did not require ATP degradation. The inability of UTP and the similar potency of ADP to reproduce ATP effects indicated that ATP could function through the P2X receptor family. These results suggest that extracellular ATP may serve as an important regulatory signal to dampen IL-12 production by DCs and thus prevent exaggerated and harmful immune responses.

Adenosine Triphosphate↗
PubMed2001

Chemokine receptor expression and function in CD4+ T lymphocytes with regulatory activity.

We have investigated the chemokine receptor expression and migratory behavior of a new subset of nickel-specific skin-homing regulatory CD4(+) T cells (Th(IL-10)) releasing high levels of IL-10, low IFN-gamma, and undetectable IL-4. These cells inhibit in a IL-10-dependent manner the capacity of dendritic cells to activate nickel-specific Tc1 and Th1 lymphocytes. RNase protection assay and FACS analysis revealed the expression of a vast repertoire of chemokine receptors on resting Th(IL-10), including the Th1-associated CXCR3 and CCR5, and the Th2-associated CCR3, CCR4, and CCR8, the latter at higher levels compared with Th2 cells. The most active chemokines for resting Th(IL-10), in terms of calcium mobilization and in vitro migration, were in order of potency: CCL2 (monocyte chemoattractant protein-1, CCR2 ligand), CCL4 (macrophage-inflammatory protein-1beta, CCR5 ligand), CCL3 (macrophage-inflammatory protein-1alpha, CCR1/5 ligand), CCL17 (thymus and activation-regulated chemokine, CCR4 ligand), CCL1 (I-309, CCR8 ligand), CXCL12 (stromal-derived factor-1, CXCR4), and CCL11 (eotaxin, CCR3 ligand). Consistent with receptor expression down-regulation, activated Th(IL-10) exhibited a reduced or absent response to most chemokines, but retained a significant migratory capacity to I-309, monocyte chemoattractant protein-1, and thymus and activation-regulated chemokine. I-309, which was ineffective on Th1 lymphocytes, attracted more efficiently Th(IL-10) than Th2 cells. I-309 and CCR8 mRNAs were not detected in unaffected skin and were up-regulated at the skin site of nickel-allergic reaction, with an earlier expression kinetics compared with IL-10 and IL-4. Results indicate that skin-homing regulatory Th(IL-10) lymphocytes coexpress functional Th1- and Th2-associated chemokine receptors, and that CCR8/I-309-driven recruitment of both resting and activated Th(IL-10) cells may be critically involved in the regulation of Th1-mediated skin allergic disorders.

CD4-Positive T-Lymphocytes↗
PubMed2001

T-cell subpopulations in the development of atopic and contact allergy.

Remarkable progress has been made in our understanding of the pathogenesis of skin diseases mediated by T cells. T-cell subsets responsible for the expression and regulation of allergic contact dermatitis to small chemicals or 'haptens' have been defined further, and the dynamics of T cells involved in the pathogenesis of atopic dermatitis have been clarified. In addition, studies are beginning to reveal the important contribution of skin resident cells to atopic dermatitis and the underlying molecular mechanisms.

Animals↗
PubMed2001

Effector and regulatory T cells in allergic contact dermatitis.

Allergic contact dermatitis is a prototypic T-cell-mediated disease that has a socio-economic impact in industrialized countries. Here, Andrea Cavani and colleagues highlight recent developments in the T-cell-based effector and regulatory mechanisms of this common skin disorder.

Dermatitis, Allergic Contact↗
PubMed2001

A cytokine-to-chemokine axis between T lymphocytes and keratinocytes can favor Th1 cell accumulation in chronic inflammatory skin diseases.

The recruitment of T cells into the skin is regulated by chemokines released by resident cells. In this study, we found that normal human keratinocytes activated with Th1-derived supernatant (sup) expressed early (6-12 h) IP-10/CXCL10, MCP-1/CCL2, IL-8/CXCL8, and I-309/CCL1 mRNAs and with slower kinetics (24-96 h), RANTES/CCL5 and MDC/CCL22 mRNAs. Upon stimulation with the Th1 sup, keratinocytes secreted high levels of RANTES, IP-10, MCP-1, and IL-8 and moderate levels of I-309 and MDC. Although much less efficiently, Th2 sup could also induce keratinocyte expression of IL-8, IP-10, RANTES, and MCP-1 but not of I-309 and MDC. TARC/CCL17 was not significantly induced by any stimuli. Sup from keratinocytes activated with Th1-derived cytokines elicited a strong migratory response of Th1 cells and a limited migration of Th2 cells, whereas sup from Th2-activated keratinocytes promoted a moderate migration of Th1 and Th2 lymphocytes. Thus, keratinocytes appear considerably more sensitive to Th1- than to Th2-derived lymphokines in terms of chemokine release and can support the preferential accumulation of Th1 lymphocytes in the skin.

Antibodies, Monoclonal↗
PubMed2000

Disparate cytotoxic activity of nickel-specific CD8+ and CD4+ T cell subsets against keratinocytes.

Allergic contact dermatitis (ACD) is the result of an exaggerated immune reaction to haptens mediated by skin-homing T cells, but the effector mechanisms responsible for the tissue damage are poorly understood. Here we studied the capacity of distinct subsets of hapten-specific T cells to induce apoptosis in autologous keratinocytes. Skin- and blood-derived nickel-specific CD8+ T cytotoxic 1 (Tc1) and Tc2 clones as well as CD4+ Th1 and Th2 expressed the cutaneous lymphocyte-associated Ag and exhibited strong MHC-restricted cytotoxicity against nickel-coupled B lymphoblasts, as detected by the [3H]TdR release assay. Both Tc1 and Tc2 clones, but not CD4+ T cells, displayed a significant cytotoxic activity against resting nickel-modified keratinocytes. Following IFN-gamma treatment, keratinocytes expressed MHC class II and ICAM-1 and became susceptible to Th1-mediated, but not Th2-mediated, cytotoxicity. The molecules of the two major cytotoxic pathways, Fas ligand (FasL) and perforin, were expressed by Tc1, Tc2, and Th1 cells, whereas Th2 cells expressed only FasL. Experiments performed in the presence of specific inhibitors of the perforin (concanamycin A) and FasL (brefeldin A) pathway indicated that perforin-mediated killing dominated in Tc1 and Tc2, and FasL-mediated cytotoxicity prevailed in Th2 clones, with a more heterogeneous behavior in the case of Th1 cells. Finally, perforin mRNA was expressed in ACD lesional skin, as assessed by RT-PCR analysis. In aggregate, our results indicate that keratinocytes can be target of multiple hapten-specific CTL responses, that may have distinct roles in the epidermal injury during ACD.

B-Lymphocytes↗
PubMed2000

IL-4 enhances keratinocyte expression of CXCR3 agonistic chemokines.

IFN-induced protein of 10 kDa (IP-10), monokine induced by IFN-gamma (Mig), and IFN-inducible T-cell alpha-chemoattractant (I-TAC) belong to the non-glutamate-leucine-arginine motif CXC chemokine family and act solely through the CXCR3 receptor for potent attraction of T lymphocytes. In this study, we evaluated the capacity of the T cell-derived cytokines IL-4, IL-10, and IL-17 to modulate IP-10, Mig, and I-TAC in cultured human keratinocytes and CXCR3 expression in T cells from allergic contact dermatitis (ACD). IL-4, but not IL-10 or IL-17, significantly up-regulated IFN-gamma- or TNF-alpha-induced IP-10, Mig, and I-TAC mRNA accumulation in keratinocytes and increased the levels of IP-10 and Mig in keratinocyte supernatants. Immunohistochemistry of skin affected by ACD revealed that >70% of infiltrating cells were reactive for CXCR3 and that CXCR3 staining colocalized in CD4+ and CD8+ T cells. Nickel-specific CD4+ and CD8+ T cell lines established from ACD skin produced IFN-gamma and IL-4 and expressed moderate to high levels of CXCR3. Finally, CXCR3 agonistic chemokines released by stimulated keratinocytes triggered calcium mobilization in skin-derived nickel-specific CD4+ T cells and promoted their migration, with supernatant from keratinocyte cultures stimulated with IFN-gamma and IL-4 attracting more efficaciously than supernatant from keratinocytes activated with IFN-gamma alone. In conclusion, IL-4 exerts a proinflammatory function on keratinocytes by potentiating IFN-gamma and TNF-alpha induction of IP-10, Mig, and I-TAC, which in turn may determine a prominent recruitment of CXCR3+ T lymphocytes at inflammatory reaction sites.

Adjuvants, Immunologic↗
PubMed2000

Interleukin-17 is produced by both Th1 and Th2 lymphocytes, and modulates interferon-gamma- and interleukin-4-induced activation of human keratinocytes.

Interleukin-17 is a T-cell-derived cytokine, detected in skin affected by allergic contact dermatitis and psoriasis, which regulates keratinocyte expression of adhesion molecules and chemokines. In this study, we have analyzed whether interleukin-17 production segregates with a particular T helper (Th) cell subset, and have examined the capacity of interleukin-17 to modulate the activation of keratinocytes induced by Th1 and Th2 cytokines. A panel of 80 nickel-specific CD4+ T cell clones (36 Th0, 30 Th1, and 14 Th2) was isolated from peripheral blood or lesional skin of allergic contact dermatitis patients. Significant amounts (> 50 pg per ml) of interleukin-17 were released by about 50% of activated Th0, Th1, and Th2 cells. Interleukin-17 alone and in cooperation with interleukin-4, or to a lesser extent with interferon-gamma, decreased the interleukin-1 receptor antagonist to interleukin-1alpha ratio in the supernatants as well as in cell lysates from keratinocytes. In addition, interleukin-17 stimulated the release of growth-regulated oncogene-alpha, granulocyte-macrophage colony stimulating factor, and interleukin-6, with synergistic or additive effects when used together with interferon-gamma or interleukin-4. Interleukin-17 and interleukin-4 also increased stem cell factor release, a function that was inhibited by interferon-gamma. Moreover, interleukin-17 and interleukin-4 enhanced interferon-gamma-induced expression of intercellular adhesion molecule 1, but not CD40, on keratinocytes. The constitutive expression of interleukin-17 and interferon-gamma receptors on keratinocytes was not modulated by interleukin-17, interferon-gamma, or interleukin-4, whereas the interleukin-4 receptor was significantly downregulated by interferon-gamma. As a whole, the results indicate that interleukin-17 can participate relevantly in T-cell-mediated skin immune responses by amplifying both interferon-gamma- and interleukin-4-induced activation of keratinocytes.

Chemokine CXCL1↗
PubMed2000

Human CD4+ T lymphocytes with remarkable regulatory functions on dendritic cells and nickel-specific Th1 immune responses.

The contribution of T helper (Th) and T cytotoxic (Tc) type 1 lymphocytes in the expression of allergic contact dermatitis to haptens has been amply documented. Conversely, the existence of T cell-based regulatory mechanisms has been poorly investigated. Here, we examined the properties of a subset of nickel-specific CD4+ T cells displaying the cytokine profile (IL-10 , IL-5 , IFN-gamma+/-, IL-4+/-) of T regulatory cells 1 (Tr1) and with the potential to down-modulate immune responses to nickel. Tr1 clones were isolated from skin challenged with NiSO4 and peripheral blood of nickel-allergic patients, and from the blood of healthy individuals. Tr1 clones expressed CD25, CD28, CD30, CD26, and the IL-12 receptor beta2 chain upon activation, whereas the lymphocyte activation antigen-3 was present on 50% of the clones. Monocytes precultured with Tr1 cells in the presence of nickel, or treated with Tr1-derived supernatant, exhibited a markedly diminished capacity to stimulate nickel-specific Th1 responses. Tr1 supernatants also blocked the differentiation of dendritic cells (DC) from monocytes, as well as DC maturation and IL-12 production induced by lipopolysaccharide. As a consequence, the ability of DC to stimulate nickel-specific Th1 and Tc1 responses was greatly impaired. These inhibitory effects were completely prevented by IL-10, but not IL-5, neutralization. In aggregate, the results indicate that Tr1 cells can potently regulate the expression of Th1-mediated allergic diseases via release of IL-10.

Adult↗
PubMed2000

Human dendritic cells are superior to B cells at presenting a major histocompatibility complex class II-restricted heterologous antigen expressed on recombinant Streptococcus gordonii.

Bacteria are being actively investigated as vaccine carriers for inducing or boosting protective immune responses. In this study, human monocyte-derived dendritic cells (DCs) and normal B cells were compared for their capacity to present the C fragment of tetanus toxin (TTFC), expressed on the surface of recombinant Streptococcus gordonii, to specific CD4(+) T lymphocytes. DCs were more efficient than B cells at presenting soluble TTFC and remarkably more capable of presenting bacterium-associated TTFC both in terms of the amount of antigen required to obtain a given T-cell response and on a per-cell basis. This difference was associated with a much lower capacity of B cells to endocytose soluble TTFC and phagocytose recombinant S. gordonii. In addition, S. gordonii induced the phenotypic maturation of DCs but not of B cells. The results thus indicate that DCs but not B cells play a crucial role in the amplification of class II-restricted immune responses induced by immunization with recombinant gram-positive bacteria.

Antigen Presentation↗
PubMed1999

Human dendritic cells very efficiently present a heterologous antigen expressed on the surface of recombinant gram-positive bacteria to CD4+ T lymphocytes.

Recombinant Streptococcus gordonii expressing on the surface the C-fragment of tetanus toxin was tested as an Ag delivery system for human monocyte-derived dendritic cells (DCs). DCs incubated with recombinant S. gordonii were much more efficient than DCs pulsed with soluble C-fragment of tetanus toxin at stimulating specific CD4+ T cells as determined by cell proliferation and IFN-gamma release. Compared with DCs treated with soluble Ag, DCs fed with recombinant bacteria required 102- to 103-fold less Ag and were at least 102 times more effective on a per-cell basis for activating specific T cells. S. gordonii was internalized in DCs by conventional phagocytosis, and cytochalasin D inhibited presentation of bacteria-associated Ag, but not of soluble Ag, suggesting that phagocytosis was required for proper delivery of recombinant Ag. Bacteria were also very potent inducers of DC maturation, although they enhanced the capacity of DCs to activate specific CD4+ T cells at concentrations that did not stimulate DC maturation. In particular, S. gordonii dose-dependently up-regulated expression of membrane molecules (MHC I and II, CD80, CD86, CD54, CD40, CD83) and reduced both phagocytic and endocytic activities. Furthermore, bacteria promoted in a dose-dependent manner DC release of cytokines (IL-6, TNF-alpha, IL-1beta, IL-12, TGF-beta, and IL-10) and of the chemokines IL-8, RANTES, IFN-gamma-inducible protein-10, and monokine induced by IFN-gamma. Thus, recombinant Gram-positive bacteria appear a powerful tool for vaccine design due to their extremely high capacity to deliver Ags into DCs, as well as induce DC maturation and secretion of T cell chemoattractans.

Antigen Presentation↗
PubMed1999

Cross-linking of membrane CD43 mediates dendritic cell maturation.

CD43/leukosialin is a major sialoglycoprotein of the dendritic cell (DC) surface, which can regulate cell adhesion and has the potential to mediate cell activation signals. Monocyte-derived DC transiently incubated with the anti-CD43 mAb, MEM-59, or with F(ab')2 fragments, but not with monovalent Fab fragments or control IgG, 24 h later showed increased levels of membrane HLA-DR, CD54, CD40, CD80, CD86, and CD83. In parallel, CD43 cross-linking induced synthesis and release of IL-1beta, IL-6, TNF-alpha, IL-12, and IL-10. CD43 ligation inhibited the endocytic activity of DC, and enhanced the capacity of DC to stimulate T cell proliferation in the primary allogeneic and autologous MLR assay. In addition, anti-CD43-treated DC were less efficient at presenting native HIV-1 reverse transcriptase to a specific CD4+ T cell clone, whereas presentation of the reverse transcriptase 55-72 peptide to the same clone was increased. Finally, MEM-59 or its F(ab')2 fragments elicited a rise in intracellular free calcium and tyrosine phosphorylation of a 25-kDa protein in DC. The results thus indicate that CD43 cross-linking with specific ligands induces activation and functional maturation of DC.

Antibodies, Monoclonal↗
PubMed1999

IL-17 is produced by nickel-specific T lymphocytes and regulates ICAM-1 expression and chemokine production in human keratinocytes: synergistic or antagonist effects with IFN-gamma and TNF-alpha.

IL-17 is a novel T cell-derived cytokine that can regulate the functions of a variety of cell types. In this study, we investigated whether hapten-specific T cells isolated from patients with allergic contact dermatitis (ACD) to nickel produce IL-17 and the effects of IL-17 alone or in combination with IFN-gamma or TNF-alpha on the immune activation of keratinocytes. Skin affected with ACD to nickel and skin-derived, nickel-specific CD4+ T cell lines expressed IFN-gamma, TNF-alpha, and IL-17 mRNAs. Four of seven nickel-specific CD4+ T cell clones positive for the skin-homing receptor, cutaneous lymphocyte-associated Ag, were shown to corelease IL-17, IFN-gamma, and TNF-alpha. In contrast, two nickel-specific CD8+ T cell clones failed to synthesize IL-17. Normal human keratinocytes were found to express constitutively the IL-17 receptor gene. IL-17 specifically and dose-dependently augmented IFN-gamma-induced ICAM-1 expression on keratinocytes at both the mRNA and the protein level, whereas HLA-DR, MHC class I, and CD40 levels were not modulated by IL-17. On the other hand, IL-17 alone did not affect ICAM-1 or enhance TNF-alpha-induced ICAM-1. In addition, IL-17, both directly and in synergism with IFN-gamma and/or TNF-alpha, stimulated synthesis and release of IL-8 by keratinocytes. In contrast, IFN-gamma- and TNF-alpha-induced production of RANTES was markedly inhibited by IL-17, and the synthesis of macrophage chemotactic protein 1 was not changed. Taken together, the results suggest that IL-17 is an important player of T cell-mediated skin immune responses, with synergistic or antagonist effects on IFN-gamma- and TNF-alpha-stimulated keratinocyte activation.

Adjuvants, Immunologic↗
PubMed1998

Interferon-gamma-stimulated human keratinocytes express the genes necessary for the production of peptide-loaded MHC class II molecules.

Keratinocytes exposed to interferon (IFN)-gamma synthesize major histocompatibility complex class II antigens both in vivo and in vitro; however, the expression of class II accessory genes has not yet been investigated. In this study, we examined the capacity of normal human keratinocytes activated with IFN-gamma to express HLA-DR, HLA-DM, and invariant chain genes as well as two major transcription regulatory genes, class II transactivator and RFX5. Cultured keratinocytes were shown to synthesize low levels of DM alpha, invariant chain p33, and RFX5 transcription factor. Upon treatment with IFN-gamma, expression of RFX5, DM alpha, and invariant chain p33 mRNA increased, whereas class II transactivator mRNA appeared de novo, followed by the expression of DR alpha, DMbeta, and invariant chain p41 genes. Western blot analysis showed that both p33 and p41 invariant chain forms and DM became detectable in keratinocytes after stimulation with IFN-gamma, with a higher p41/p33 ratio compared with Raji B cells. Finally, HLA-DR molecules present on IFN-alpha-treated keratinocytes were shown to be remarkably resistant to sodium dodecyl sulfate denaturation at room temperature, a feature that class II molecules acquire when their groove is properly loaded with peptide. These results suggest that human keratinocytes activated with IFN-gamma possess the biochemical requirements for the generation of functional class II peptide complexes.

Adult↗
PubMed1998

Contact hypersensitivity in MHC class II-deficient mice depends on CD8 T lymphocytes primed by immunostimulating Langerhans cells.

Studies to determine if CD4+ and/or CD8+ T cells are critical for the initiation and propagation of contact hypersensitivity (CHS) reactions have yielded conflicting results regarding their roles. We studied the induction and expression of CHS to trinitrochlorobenzene (TNCB) using major histocompatibility complex class II-deficient mice that display normal numbers of CD8+ T cells but lack CD4+ T cells. CHS to TNCB, detected as an increase in ear thickness 24 h after epicutaneous challenge, was significantly enhanced in major histocompatibility complex class II-deficient mice compared with wild-type controls. Ear swelling responses in major histocompatibility complex class II-deficient mice were decreased by treatment with anti-CD8 antibody or by injection of wild-type CD4+ T cells. To further characterize mechanisms involved in the initiation of CHS responses, phenotypical and functional characteristics of both freshly isolated and cultured Langerhans cells were studied. Like Langerhans cells from wild-type controls, Langerhans cells from major histocompatibility complex class II-deficient mice upregulated B7-1 and B7-2 costimulatory molecules and enhanced major histocompatibility complex class I expression upon short-term culture. Cultured Langerhans cells induced a 3.5-fold increase in the stimulation of autologous hapten-specific CD8+ T cell proliferation compared with fresh Langerhans cells. Finally, TNP-coupled Langerhans cells from major histocompatibility complex class II-deficient mice primed naive mice to TNCB after transfer. These results demonstrate that hapten-specific CD8+ T cells are sufficient for the expression of CHS and that CD8 priming does not require the presence of CD4+ T cells or major histocompatibility complex class II antigen. Key words: CD8 lymphocytes/MHC class II deficiency.

Adoptive Transfer↗
PubMed1998

Patients with allergic contact dermatitis to nickel and nonallergic individuals display different nickel-specific T cell responses. Evidence for the presence of effector CD8+ and regulatory CD4+ T cells.

To investigate the mechanisms underlying the expression of allergic contact dermatitis, we compared the characteristics of nickel (Ni)-specific T cell responses in 10 patients with allergic contact dermatitis to Ni and in 10 healthy, nonallergic individuals. CD4+ T cells purified from peripheral blood of both allergic and nonallergic subjects proliferated similarly to NiSO4 in vitro, with the responses mostly restricted to CD4+ CD45RO+ memory T cells. In contrast, Ni-specific CD8+ T cell responses were detected only in allergic patients. Limiting dilution assay confirmed a high frequency of Ni-specific CD4+ T cells in both individual categories, and of Ni-specific CD8+ T cells in allergic patients, but not in nonallergic persons. Ni-specific CD4+ T cell clones prepared from nonallergic subjects displayed lower interferon-gamma and higher interleukin-10 production compared with T cell clones from allergic patients. The T cell skin-homing receptor, cutaneous lymphocyte-associated antigen, was expressed on the large majority of specific CD4+ clones from both the groups. Finally, Ni-specific CD8+ clones prepared from patients also expressed the cutaneous lymphocyte-associated antigen receptor, and released high interferon-gamma and no interleukin-4. In aggregate, the results suggest that the presence of specific CD8+ T cells and a distinct pattern of cytokine release (e.g., an augmented production of interleukin-10) by CD4+ T cells can be important elements in determining whether a hapten induces allergy or a silent immune response.

Adult↗