Clinical, pathologic, and immunologic features of human T-lymphotropic virus type I- associated infective dermatitis in children

Objectives: To define the clinical and laboratory features associated with infective dermatitis (ID) and confirm its association with human T-lymphotropic virus type 1 (HTLV-I). Design: A case series of patients with ID were compared with patients with atopic dermatitis (AD) which is an important disease in the differential diagnosis of ID. Setting: Patients were recruited from dermatology and pediatric clinics at the University Hospital of the West Indies and the Bustamante Children's Hospital, Kingston, Jamaica. Main Outcome Measures: Clinical and laboratory features of patients with AD were compared with those of patients with ID. Patients: Consecutive patients older than 1« years diagnosed as having ID (n=50) and AD (n=35) were enrolled based on clinical findings. Results: The mean age of patients with ID and AD were 6.9 and 7.8 years, respectively. Histologically, both disease were predominantly chronic dermatitis... Conclusion: Infective dermatitis is a distinct clinical entity associated with HTLV-I, which plays a role in the pathogenesis and immune perturbations observed.(AU)

Direct analysis of viral-specific CD8+ T cells with soluble HLA-A2/Tax11-19 tetramer complexes in patients with human T cell lymphotropic virus-associated myelopathy

Human T cell lymphotropic virus-I (HTLV-I) -associated myelopathy is a slowly progressive neurologic disease characterized by inflammatory infiltrates in the central nervous system accompanied by clonal expansion of HTLV-I-reactive CD8+ T-cells. In patients carrying the HLA-A2 allele, the immune response is primarily directed to the Tax11-19 peptide. The frequency, activation state, and TCR usage of HLA-A2/Tax11-19 binding T cells in patients with HTLV-I-associated myelopathy was determined using MHC class I tetrameters loaded with the Tax11-19 peptide. Circulating Tax11-19-reactive T cells were found at very high frequencies, approaching 1:10 circulating CD8+ T cells. T cells binding HLA-A2/Tax11-19 consisted of heterogeneous populations expressing different chemokine receptors and the IL-2R beta-chain but not the IL-2R alpha-chain. Additionally, Tax11-19-reactive CD8+ T cells used one predominant TCR beta-chain for the recognition of the HLA-A2/Tax11-19 complex. These data provide direct evidence for high frequencies of circulating Tax11-19-reactive CD8+ T cells in patients with HTLV-I-associated myelopathy.(Au)

Mononuclear cells in sickle cell disease: subpopulations and in vitro response to mitogens

The subpopulations of mononuclear cells and the lymphocyte proliferative capacity following mitogen stimulation were studied in 22 patients with homozygous sickle cell (SS) disease and 25 controls with a normal haemoglobin (AA) genotype. The total number of lymphocytes in peripheral blood samples was higher in SS patients compared to controls. Expressed as a percentage of total lymphocytes, the number of B lymphocytes (detected by membrane immunoglobulin Fluorescence) was normal and of T lymphocytes (identified by sheep erythocyte rosetting) was slightly reduced in SS disease. Expressed in absolute numbers, both B and T lymphoctes were increased. Lymphocyte proliferation measured by tritium labelled thymidine incorporation following stimulation with phytohaemaeglutin A and concanavalin A was normal. Following pokeweed mitogen stimulation, thymidine incorporation was significantly increased in SS disease although normal when expressed as a stimualtion index. These results do not suggest a major defect in cell mediated immunity in sickle cell disease. The number of circulating monocytes was increased in SS disease and correlated inversely with the number of reticulocyytes (r= -0.58, p < 0.005) (AU)

Immune responses during human schistosomiasis mansoni. III. Regulatory effect of patient sera on human lymphocyte blastogenic responses to schistosome antigen preparations

The in vitro lymphocyte blastogenesis capabilities of patients with schistosomiasis mansoni were tested against phytohemagglutinin (PHA), Candida albicans extract,and soluble preparations of schistosome eggs (SEA), adult worms (SWAP), or cercariae (CAP). When patients lymphocytes were cultured un medium which contained 5 percent human (homologous) normal (uninfected) serum, they responded well to PHA and Candida extract. The responses induced by SEA were maximal in patients with early Schistosma mansoni infections, while reactivity against SWAP and CAP increased during chronic infection. These responses, induced by the Schistosome-derived antigenic preparations,were suppressed if the homologous normal serum supplement of the culture medium was replaced with either the patient's own (autologous) serum, or that of another S. mansoni patient. All sera were heat-inactivated (56 degree C/ 30 min) prior to use. In contrast, responses against the non-specific mitogen (PHA) and the unrelated antigen (Candida extract), were not altered by these changes of the serum supplementation of the media. The degree of suppression by patient serum was not changedby increasing the serum percentage in the medium from 5 percent to 25 percent. The suppressive effects of patient sera on responses induced by SEA and SWAP were increased in relationship to the duration of the serum donor's S. mansoni infection. Preincubation of lymphocytes in suppressive patient sera for 30 min at 37 degree C did not reduce the expected level of responsiveness if the cells were subsequently cultured in homologous-normal serum supplemented medium. The data indicate that during S. mansoni infection patients develop serum component(s) which specifically interfere with the responsiveness of their lymphocytes in regard to certain schistosome-derived antigenic preparations. The immunoregulatory events described could participate in the modulation of immunopathology, the maintenance of chronic worm survival and the prevention of full expression of protective immune responses. (AU)

Immune response during human schistosomiasis mansoni. II. Occurrence of eosinophil-dependent cytotoxic antibodies in relation to intensity and duration of infection

Plasma samples from St. Lucians were tested for the presence of antibodies which cooperate in vitro with normal human luekocytes in causing cytotoxic damage to schistosomula of Schistosoma mansoni. The in vitro antibody activity, which has been previosly shown to depend on eosinophil effector cells was detected in 56 percent of the individuals with known, current S. mansoni infections and in 14 percent of control subjects from the same endemic area. Quantitatively, eosinophil dependent cytoxic antibody (EDCA) activity, when expressed as the maximum amount of damage to schistosomula induced at high plasma concentration, correlated significantly with the intensity of S.mansoni infection as detemined by fecal egg count, the highest levels of activity occuring in patients with stool counts of 60 eggs/ml or greater. In addition, plasma ECDA activity was found to correlate with the in vitro blastogenic responsiveness of patients' lympjocytes to three different parasite antigen preparations. In contrast, titrations of ECDA activity failed to reveal a relationship between ECDA titer and the most recent egg count performned on each subjects. However, a significant correlation was observed when titers were compared to egg counts averaged over a 3-year period. Neither maximal ECDA activity nor titer was found to correlate with the duration of known schistosome infection (AU)