C Simonelli

Cytokine production by allergen (Der pI)-specific CD4+ T cell clones derived from a patient with severe atopic disease

SummaryTwenty-four T cell clones (TCC) specific for purifiedDermatophagoides pteronyssinus group I allergen (Der pI) were established from the peripheral blood of a patient with severe atopic disease and assessed for cytokine production in response to stimulation with both phorbol 12-myristate 13-acetate and anti-CD3 monoclonal antibody. All Der pI-specific TCC produced high amounts of interleukin (IL)-4 in association with IL-3, IL-5 and granulocyte monocyte-colony stimulating factor (GM-CSF), whereas they produced variable amounts of IL-2 and virtually no interferon-γ. These data support the hypothesis that atopy is associated with preferential activation of type 2 T helper cells and suggest a deregulation in the function of the IL-3, IL-4, IL-5 and GM-CSF gene cluster in subjects with severe atopic disorders.

Role of T Cells in the Pathogenesis of Hodgkin's Disease

Publisher Summary Despite the great progress that has been achieved in recent years in the diagnosis and treatment of Hodgkins lymphoma, the etiopathogenesis of this disease still remains obscure. Definite proof that Hodgkins disease (HD) is a malignant neoplasm, albeit a remarkably atypical one, has been provided during the past two decades by a number of cytogenetic, immunological, and molecular biology studies. Several fundamental issues, however, still remain open. They include the genesis of the immune deficiency, the nature of the normal counterpart of the neoplastic cells, and the role of other tumor-infiltrating lymphocytes. This chapter describes the immunological alterations found in untreated HD patients, mainly focusing on those involving the T and B cell compartments. The chapter also discusses the hypotheses on the origin of Reed–Sternberg (RS) cells and describes the role of the cells surrounding them in involved lymphoid organs.

The IgE response in atopy and infections

The IgE antibody system represents an important defense mechanism against offending agents coming from the respiratory and gastrointestinal tracts. The human pathological condition most commonly associated with hyperproduction of IgE is atopy, the familial allergic disorder of immediate-type hypersensitivity to environmental allergens. Dysregulation of IgE synthesis has also been observed in clinical disorders often associated with immunodeficiency and/or infections, such as the Hyper-lgE syndromes (1), parasitic infestations, some primary and secondary immunodeficiencies (2, 3), AIDS (4), the acute phase of GVHD (5). Therefore, the understanding of mechanisms involved in IgE regulation is of primary importance in order to define the alterations responsible for allergic diseases, as well as other pathological conditions characterized by hyperproduction of IgE. In the first part of this paper we have summarized the mechanisms that regulate the synthesis of IgE in humans. In the second part, we discuss the pathophysiological aspects of IgE dysregulation in disorders characterized by hyperproduction of IgE.

Increased production of IgE protein and IgE antibodies specific for fungal antigens in patients with the acquired immunodeficiency syndrome

SummaryLevels of IgE protein and IgE antibodies specific for 8 different allergenic extracts were measured in the serum of a large series of patients infected by the human immunodeficiency virus (HIV) and in HIV-seronegative subjects belonging to the same risk groups (intravenous drug-users, homosexual men and hemophiliacs). The proportion of subjects showing elevated IgE levels was higher among HIV-infected patients with group IV disease than among HIV-infected patients with group II–III diseases or seronegative individuals. In addition, many HIV-infected patients with elevated IgE levels showed the presence in their serum of IgE antibodies specific for fungal antigens.

Both CD8+ and CD16+ human T cell clones can provide B cell help for immunoglobulin production

SummaryThe functional properties of two CD4+CD8−CD16−, five CD4−CD8+CD16− and three CD4−CD8−CD16+ human T cell clones were compared. All CD4− T cell clones displayed strong cytolytic activity in the lectin-dependent lytic assay against the P815 murine mastocytoma cell line, but only the CD4−CD8−CD16+ T cell clones exhibited lytic activity against the natural killer-sensitive K562 cell line. Upon activation with anti-CD3 monoclonal antibody, all T cell clones were able to support IgM and IgA synthesis in autologous B cells. Both CD4+ and CD4− T cell clones required cell-to-cell interaction with the B cells in order to exert their helper activity for immunoglobulin production. However, unlike CD4+, CD4−CD8+CD16− and CD4−CD8−CD16+ T cell clones provided helper function for immunoglobulin synthesis only when low T/B cell ratios were used in culture. At higher T/B cell ratios, there was a decline in the B cell helper activity of CD4− T cell clones that was probably related to the expression of cytolytic capacity against the antigen-presenting B cell. These data support the notion that under certain experimental conditions even cytotoxic T lymphocytes and natural killer cells may provide B cell helper function.

In vitro Infection with hiv of antigen-specific t cell clones derived from hiv-seronegative individuals. effects on cytokine production and helper function

SummaryThree human T cell clones (TCC) specific for purified protein derivative of Mycobacterium tuberculosis were incubated in the presence of polybrene and phytohemagglutinin with irradiated mononuclear cells from one individual exhibiting seropositivity for human immunodeficiency virus (HIV) and high levels of circulating p24 antigen. After three weeks, TCC showed HIV integration in their DNA, as shown by polymerase chain reaction analysis and Southern blot technique. All the three HIV-infected TCC maintained their ability to recognize the specific antigen, even if their proliferative ability was reduced. The ability of the HIV-infected TCC to produce IL-2, IL-4 and IFN-y in response to phorbol myristate acetate plus anti-CD3 monoclonal antibody was decreased, whereas their ability to produce TNF-α was unaffected or even enhanced. Two our. of the three HIV-infected TCC showed the ability to provide helper function for polyclonal immunoglobulin production when cocukured with autologous B cells in the absence of any stimulant. These data suggest that in vitro infection of normal human TCC may provide a useful model for the study of immunological alterations induced by HIV.

CD4 + T Cells from Lymph Nodes Involved by Hodgkin's Disease Showing Response in Autologous Mixed Lymphocyte Reaction, are Polyclonal.

Thirteen CD4 + T cell clones (TCCs) showing autologous mixed lymphocyte reaction (AMLR) and 12 CD4 + AMLR-negative TCCs derived from involved lymph nodes (LN) of 4 untreated patients with newly-diagnosed Hodgkins disease (HD) were analyzed for some functional activities and for T cell receptor (TCR) gamma and beta gene rearrangement The majority of the AMLR-positive-, but only two AMLR-negative TCCs showed cytolytic potential when assayed by a lectin-dependent assay. In addition, the proportion of clones able to produce interleukin 2 (IL-2) was higher among AMLR-positive- than AMLR-negative TCCs and the amount of IL-2 synthesized by AMLR-positive TCCs was significantly greater than that of AMLR-negative TCCs. In contrast, no difference in the profile of interleukin 4 (IL-4) and interferon-gamma (IFN-γ) production between AMLR-positive- and AMLR-negative TCCs was detected When AMLR-positive TCCs were analysed for their TCR beta and gamma gene rearrangements, a highly heterogeneous pattern was found. More importantly, TCCs derived from the same donor and displaying the same kind of TCR beta and gamma gene rearrangement showed different patterns of rearrangements, suggesting that CD4 + cells from LN involved by HD, displaying such an unusual functional profile, are polyclonal.