CD3+/CD30+ circulating T lymphocytes are markedly increased in older subjects with Down's syndrome (Trisomy 21).

CD3+/CD30+ circulating T lymphocytes were found to be increased in the blood of individuals with Down's syndrome (DS; trisomy 21). This finding appears to be related to age as the numbers of CD3+/CD30+ T cells were dramatically enhanced in the circulation of older DS subjects. Since CD30 antigen expression is considered to be a marker of T-helper-2 (Th-2) activation, and Th-2+ cells are associated with certain human pathologies, our data may in some way explain the enhanced susceptibility of DS patients to infections, malignant diseases and autoimmunity.

Soluble CD30 antigen in human colostrum.

It is now well established that the CD30 glycoprotein is a surface antigen expressed by activated T cells producing T-helper (Th)-2-type lymphokines. Mounting laboratory evidence, however, suggests that CD30 expression is not confined to a functionally restricted subset of T cells, but also identifies activated cells with a Th-1 and Th-0 pattern of cytokine secretion. CD30-bearing T lymphocytes release a soluble form of the molecule (sCD30), which can be detected both in vitro and in vivo. In the present study, very high levels of sCD30 were found in colostrum from 20 puerperal women, but not in autologous and heterologous (nonpregnant women) blood samples. These data strongly support an involvement of CD30+ T cells in the immune processes which take place at the level of the mammary gland during pregnancy and lactation. Passively transferred immune components such as immunoglobulins, cytokines, macrophages, natural killer cells, granulocytes and memory/activated T cells, all of which may help the baby to fight off infections, have been revealed in human breast milk. However, how Th-2-type cytokine-secreting T cells or other T-cell types help to endow the congenitally immunocompromised newborn infant with extrinsic immunological support remains an open question.

CD26 and CD31 surface antigen expression on human colostral T cells.

The expression levels of CD26 and CD31 surface antigens, two adhesion/activation molecules with helper and suppressor activities, respectively, were found to be significantly higher on human colostral T cells (CD3+) than in autologous peripheral blood samples. These findings provide further phenotypical evidence that immune system T lymphocytes are compartmentalized in the mammary gland late in pregnancy and during lactation. The question of whether these overexpanded T lymphocyte populations in breast milk modulate in situ, either by enhancing or suppressing, the cellular and/or humoral immune response of the suckling infant remains to be answered. Additional studies are, therefore, needed to explore this intriguing field concerning the immunology of the colostrum.

CD26 surface antigen expression on peripheral blood T lymphocytes from children with Down's syndrome (trisomy 21).

A phenotypical analysis carried out by two-colour flow cytometry showed that the proportion of circulating CD4+ T lymphocytes co-expressing the membrane-associated ectoenzyme dipeptidyl peptidase IV (CD26 antigen), a functional collagen receptor involved in T-cell triggering through its interaction with the CD45 protein tyrosine phosphatase, was significantly lower in 28 children with non-translocated trisomy 21 (Down's syndrome) (DS) than that calculated in the bloodstream of 27 age- and sex-matched healthy controls. Agonist anti-CD26 monoclonal antibodies (MoAbs), such as anti-1F7, not only modulate the surface expression of this molecule, but also enhance the proliferative activity of normal human T cells via the CD3- and CD2-mediated activation pathways. T-lymphocyte proliferation induced by antigen or polyclonal T-cell activators, including anti-CD3 or -CD2 MoAbs, is severely impaired in DS. Although the physiological ligand of CD26 surface structure is unknown, the fact that CD4+ T lymphocytes found in the blood of trisomic subjects are mostly CD26- (anti-1F7-) suggests that their faulty mitogenic response may be due to phenotypical and, perhaps, strictly correlated functional abnormalities.

Lymphocytes bearing the gamma delta T-cell receptor in acute toxoplasmosis.

Although the relative and absolute numbers of CD3+ cells (T lymphocytes) were similar in eight children with acquired Toxoplasma gondii infection and 10 uninfected age- and sex-matched healthy controls, the proportion of cells bearing the gamma delta T-cell receptor was significantly higher in the subjects with acute toxoplasmosis. The great majority of gamma delta T cells from the infected patients expressed covalently bound gamma delta chains on their surface, i.e. were BB3+ lymphocytes. Since the gamma delta T-cell subsets exert both restricted and unrestricted major histocompatibility complex cytotoxicity, further research is needed to elucidate the role of gamma delta T cells in the control of this coccidian protozoan infection.

Interferon-gamma (r-IFN-gamma) induced activation of alveolar macrophages (AM) from anergic patients with chronic obstructive pulmonary disease (COPD).

Forty-six anergic patients (37 males and 9 females, age range 55-79 yr) were selected from ninety-one patients suffering from COPD due to frequent exacerbations and impaired delayed cutaneous reactivity (43.9%). The phenotype of circulating lymphocytes, their proliferative response to a panel of polyclonal T-cell activators and the candidacidal activity (CA) of circulating PMNs (polymorphonuclear cells) were measured. In 13 patients presenting a defective CA of circulating PMNs, the in vitro response of alveolar macrophage CA to r-IFN-gamma was also determined. We found: 1) a significant reduction in the CL response to PHA in COPD patients vs controls; 2) a low PMN-CA in 23 (57%) COPD patients; 3) a non-significant difference in phenotype analysis in patients and controls; 4) lower CA of AMs in COPD patients than in controls; 5) restoration in vitro of CA by r-IFN-gamma in the group of anergic COPD patients presenting depressed CA. We conclude that a defective cell-mediated immunity could be the basis of the enhanced susceptibility to infectious exacerbations in many COPD patients and that, in vitro, it could be reversed by r-IFN-gamma treatment.

Human breast milk T lymphocytes display the phenotype and functional characteristics of memory T cells.

Naive (unsensitized) and memory (antigen-primed) T cells can be phenotypically distinguished on the basis of the high or low intensity with which they express a number of immunologically relevant lymphocyte membrane antigens, including CD45R, CDw29, UCHL1, LFA-1, LFA-3, CD2 and Pgp-1. Here we report that in contrast to the two major T cell subsets found in the blood, milk T lymphocytes are almost exclusively composed of the one which exhibits the CD45Rlow, CDw29, UCHL1, LFA-1high memory T cell phenotype. In addition, while milk and autologous blood cells expressed similar levels of CD3 surface antigens, CD2 and ICAM-1 expression was approximately twofold greater on the milk T lymphocytes. This agrees with the finding that whereas colostrum T cells respond poorly to PHA, they proliferate and produce interferon-gamma normally when stimulated with either the anti-CD3 or anti-CD2 monoclonal antibodies. The selective colonization of the mammary gland during lactation by a population of T lymphocytes which displays the phenotype and functional characteristics of memory T cells may be one of the mechanisms whereby the suckling infant benefits form its mother's immunological experience.

Activation of cord T lymphocytes. II. Cellular and molecular analysis of the defective response induced by anti-CD3 monoclonal antibody.

Despite the fact that the percentage of circulating CD3-positive cells is similar in cord and adult blood, the proliferative response induced by anti-CD3 monoclonal antibody (mAb) was impaired in the majority of human cord peripheral blood mononuclear cell (PBMC) samples we tested. The cell proliferative defect was associated with low interleukin 2 (IL 2) gene expression and scant IL 2 production. However, interleukin 2 receptor was fully expressed at both the mRNA and protein levels. Such a finding is consistent with the observation that exogenous recombinant IL 2 is able to boost the anti-CD3-mediated response of cord PBMC. Furthermore, when anti-CD3 and phorbol myristate acetate (PMA) were added together, they exerted a very marked synergistic effect on both the proliferation of, and IL 2 production by, cord PBMC. The addition of allogeneic antigen presenting cells plus soluble anti-CD3 or Sepharose-coupled anti-CD3 mAb to the cord T cell cultures had no significant effect on proliferation, whereas both elicited good mitogenesis of adult T cells. Moreover, addition of exogenous recombinant interleukin 1 to anti-CD3-stimulated T cells failed to trigger any proliferation in either adult or cord samples. Since the combination of PMA and calcium ionophore A23187 is effective in triggering optimal proliferation of cord T cells, the defect would seem to be associated with a failure in transmembrane transduction of the activation signals provided by the anti-CD3 stimulus for the cord T cell.

T-cell response to phorbol ester PMA and calcium ionophore A23187 in Down's syndrome.

The proliferative response of purified T cells to anti-CD2 monoclonal antibodies (T112 plus T113) was found to be markedly reduced in 12 subjects with Down's syndrome (DS). The addition of phorbol ester PMA, which activates Ca2+/phospholipid-dependent enzyme protein kinase C, or calcium ionophore A23187, which increases intracytosolic free Ca2+ concentration, enhanced, but did not normalize, the defective anti-CD2-mediated T-cell mitogenesis. In contrast, the proliferation of resting lymphocytes from trisomic patients was comparable to that of the control cells when PMA and A23187 were used as co-blastogenic reagents. Because PMA and A23187 together bypass the early activation pathways and promote T-cell growth through the direct induction of membrane interleukin 2 (IL-2) receptor expression and IL-2 synthesis and secretion, it could reasonably be hypothesized that the faulty DS T-cell activation induced by antigen or mitogen is due to a deranged transmembrane signal transduction, rather than a defect in the later intracellular events.

Anti-CD3 and anti-CD2-induced T-cell activation in primary Sjögren's syndrome.

Because T-cell dysfunctions have been reported in patients with primary Sjögren's syndrome (SS), peripheral blood mononuclear cell (PBMC) proliferation obtained with anti-CD3 and anti-CD2 monoclonal antibodies was evaluated in these patients. Anti-CD3-induced mitogenesis, which varied widely among the patients, was lower in subjects with evidence of anti-SSA and anti-SSB antibodies than in controls. Moreover, the anti-CD2-induced response was depressed in about half the patients and the nonresponders were mainly those with anti-SSA and anti-SSB antibodies. Phorbol myristate acetate, a protein kinase C activator, used alone or added to anti-CD3, induced greater proliferation in patients than in control PBMC. In contrast, exogenous recombinant interleukin 2 (rIL-2) did not significantly enhance the anti-CD2-induced response of patients' PBMC, as it did in normal PBMC. Peripheral blood and parotid T cells from a patient with well-defined primary SS and parotid enlargement also responded poorly to anti-CD2 stimulation. Exogenous rIL-2 restored T-cell proliferation only in the salivary gland cultures of this patient. The present findings suggest that there is a T-cell activation defect in subjects with primary SS, particularly in those with circulating anti-SSA and anti-SSB antibodies. In addition, the difference in the response to IL-2 of peripheral blood and parotid-infiltrating T cells would seem to indicate that T-cell subsets are differently distributed in the blood and inflammation site.

T-cell response to anti-CD2 monoclonal antibodies in Down's syndrome.

Peripheral blood mononuclear cells from 10 subjects with cytogenetically documented Down's syndrome (DS) and from 10 age- and sex-matched healthy controls were assayed for their ability to proliferate in response to phytohaemagglutinin, anti-CD3 (OKT3), or anti-CD2 (T11(2) plus T11(3] monoclonal antibodies. Interleukin 2 (IL-2) receptor expression and IL-2 production in mitogen-pulsed lymphocyte cultures was also investigated in parallel. DS cells responded poorly to all the blastogenic stimuli used in this study. Under certain experimental conditions (anti-CD3 or anti-CD2 antibody stimulation), the patients' lymphocytes expressed low levels of IL-2 surface receptors and failed to produce normal amounts of this lymphokine. Studies are currently in progress in our laboratories to determine whether these defects are due to an impairment of the early signalling events surrounding the complexing of CD3, CD2, or lectin receptors to their respective ligands.

Activation of cord T lymphocytes. I. Evidence for a defective T cell mitogenesis induced through the CD2 molecule.

A study was carried out on cord blood T cell activation via the CD2-mediated pathway. Despite similar percentages of circulating CD3+ and CD2+ cells in adult and cord blood, the proliferation of cord PBMC to the anti-CD3 mAb and cord T cells to anti-CD2 mAb were defective. The T cell CD3-surface structure was normally able to control CD2-mediated activation, as its modulation by a non-mitogenic anti-CD3 mAb blocked cord PBMC proliferation induced by anti-CD2 mAb. CD2-stimulated cord T cells did not proliferate and did not produce a significant amount of IL-2 in culture, although they expressed the IL-2R. This observation was confirmed by the optimal proliferation of CD2-induced cord T cells when rIL-2 was added. Despite the alternative T cell activation pathway is monocyte-independent in adults, the defective cord T cell activation via the CD2 molecule could also be bypassed by the addition of PMA, small amounts of either autologous or allogeneic adult and cord AC or simply rIL-1 alone. Our findings provide evidence for an intrinsic functional defect in cord CD2-mediated T cell activation, which is linked to an impaired increase of free cytoplasmic calcium, as confirmed by the effectiveness of calcium ionophore A23187 in restoring a good CD2-induced cord T cell proliferation and by measurement of cellular calcium uptake after activation via the CD2 molecule. The characteristics of cord T cells revealed by this study recall the thymocyte functional pattern and may represent functional expression of the previously described phenotypic immaturity of cord T cells.

T cell response to anti-CD3 antibody in Down's syndrome.

The non-specific mitogen phytohaemagglutinin (PHA) and an anti-CD3 (OKT3) monoclonal antibody were used to measure the lymphocyte proliferative response in blood samples from 15 subjects with Down's syndrome. Blood from 15 healthy controls closely matched for age and sex was also assayed. The mean blastogenic value in PHA stimulated patient lymphocyte cultures was similar to that calculated in the controls. In contrast, the mitogenic response of lymphocytes from patients with Down's syndrome to anti-CD3 stimulation was on average significantly reduced. Immunofluorescence studies and additional experiments carried out by using semiallogeneic (maternal) monocytes as a source of antigen presenting cells showed that the impaired anti-CD3 induced mitogenesis in Down's syndrome could not be ascribed either to a lack of binding of the antibody to the trisomic cells, or to a defective monocyte-T cell interaction. These findings help to explain the cellular basis of the immune defect in Down's syndrome.

Phenotypic heterogeneity within the circulating human neonatal T4-positive T cell subset.

An indirect immunofluorescence staining technique was employed to evaluate the TQ1 and 5/9 monoclonal antibody lymphocyte reactivity in 10 cord blood mononuclear cell (MC) preparations enriched of E-rosette-forming cells (E+). Ten adult E+ MC populations were used as controls. Unfractionated T4+ cord and adult MC positively selected by panning procedure were also assayed. The results of these experiments, taken together, suggest that there is an overexpanded neonatal T cell subset which displays a previously unrecognized immunophenotype (T4+, TQ1+, 5/9+). Whether these lymphocytes are involved in the wellknown fetal-maternal immunosuppressive mechanisms of whether they are a further example of neonatal phenotypic immaturity remains to be elucidated.

Incidence of childhood cancer in the province of Perugia (Italy).

This paper reports the incidence of childhood cancer in the Province of Perugia (Italy) in 1975-1979 and compares it with that reported in other areas in Italy and other western countries. Over the period studied the new cases of cancers in children under 15 years of age, recorded in the Province of Perugia, were 51 in males and 36 in females. The mean annual incidence rates per 100,000 were 17.93 in males and 13.51 in females so that the male to female ratio of rates was 1.33. The most common neoplasms were leukemia (4.92 per 100,000 in males and 5.25 in females), brain tumours (3.87 in males and 1.50 in females), nephroblastomas (1.40 in males and 1.50 in females), lymphomas (2.81 in males and 0.37 in females). This distribution, in general, is the same as that observed in many other white populations. However some differences in the incidence value rates between the Province of Perugia and other areas of western countries are pointed out both for the cancers as a whole and for certain histologic types.

[Infantile idiopathic pulmonary hemosiderosis. Presentation of a case]. / Emosiderosi polmonare idiopatica infantile. Presentazione di un caso.

The present report deals with a patient affected by idiopathic pulmonary hemosiderosis. The diagnosis was made by pulmonary biopsy and ultrastructural and immunological study. We are treating the patient with iron therapy and desferrioxamine.