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C Steel

Publications and source records attributed to C Steel.

26 records · Page 2Linked to original sources
PubMed1991

Immunoregulation in onchocerciasis. Functional and phenotypic abnormalities of lymphocyte subsets and changes with therapy.

To help define the immunoregulatory defects in patients with onchocerciasis, flow cytometric analysis of circulating lymphocyte subpopulations was performed in parallel with functional assays. No significant differences in CD4/CD8 ratios were seen when microfilariae-positive individuals from Guatemala were compared with Guatemalan controls. However, the infected individuals had significantly increased numbers of circulating CD4+CD45RA+ lymphocytes (mean 38.3%) when compared with controls (mean 16.0%). Coexpression of the activation marker HLA-DR was significantly increased on CD4+ cells from infected individuals. In contrast, no up-regulation of HLA-DR was seen on CD8+ or CD19+ cells. At 1 year after initiation of treatment with semiannual doses of the microfilaricide ivermectin, there were significant increases (P less than 0.05) in the percentage of CD4+CD45RA- cells, the percentage of CD4+HLA-DR+ cells, and mitogen-induced lymphokine production (IL-2, IL-4). Despite these changes, parasite-specific IL-2 and IL-4 production which had been undetectable before treatment did not manifest itself even by the 2-yr follow-up. Defects in the T-cell activation pathway in Onchocerca volvulus-infected individuals may thus exist at several independent points; a state of parasite antigen-specific tolerance appears to remain even after the relative reversal of other generalized immunoregulatory defects.

Adolescent↗
PubMed1990

B cell responses to paramyosin. Isotypic analysis and epitope mapping of filarial paramyosin in patients with onchocerciasis.

To examine the fine specificity of the human immune response to filarial paramyosin, the antigenicity of an expressed rcDNA (2.55 kb) of Dirofilaria immitis paramyosin was detailed by ELISA. Using sera from patients infected with Onchocerca volvulus, we analyzed both the entire paramyosin molecule and six subcloned fragments for their IgG, IgG subclasses, and IgE responses. Patients from both Guatemala (64% positive) and Ghana (100% positive) reacted to paramyosin with specific IgG levels above normal controls. Although there was no anti-paramyosin subclass restriction common to all patients, the IgG3 response in the Ghananians was significantly greater than that of Guatemalans (p less than 0.001). IgE anti-paramyosin responses showed positive correlations with IgG2 (p less than 0.001), IgG4 (p less than 0.002), and IgG1 (p less than 0.04) responses. Epitope mapping using the IgG response to the six subclones demonstrated preferential recognition of the amino terminal end of the molecule (nucleotides 1 to 360). IgG2 reactivity was clearly localized to the most amino-terminal 120 amino acids, and the IgG4 antibodies recognized amino acids immediately adjacent to this fragment. These studies examining the fine specificity of anti-filarial immune reactions should provide a method for understanding how parasites either evade or induce host immune responses.

Adolescent↗
PubMed1990

Phosphocholine-containing antigens of Brugia malayi nonspecifically suppress lymphocyte function.

The immunosuppressive effect of Brugia malayi antigen (BmA) on phytohemagglutinin (PHA) driven T cell proliferation was evaluated in patients with filariasis (n = 14) and compared to control individuals (n = 12). When peripheral blood lymphocytes were co-cultured with BmA and PHA, BmA markedly suppressed the T cell proliferative response to PHA in both filarial patients and control individuals in a dose-dependent manner. The suppression resulted neither from any direct toxicity of BmA nor from nonspecific absorption of the PHA mitogenic activity by BmA. The major suppressive component appears to be phosphocholine (PC), an immunodominant molecule present in abundance on filarial parasites and on circulating filarial antigen. Both purified PC as well as PC-containing antigens affinity purified from BmA were capable of suppressing the proliferative responses of co-cultured autologous lymphocytes to PHA. The suppressive activity was not abolished by mitomycin-C treatment and was greater in patients with filariasis than in normal controls, suggesting that levels of PC-containing antigens determines the magnitude of the suppressive effect of PC-antigen. Further, as induction of the suppressive activity was completely abrogated when antigen pre-treated cells were T cell-depleted, the suppressive effect appears to be mediated primarily by T cells.

Adult↗
PubMed1989

Human T-cell stimulation, molecular characterization and in situ mRNA localization of a Brugia malayi recombinant antigen.

Cellular immune responses play a major role in lymphatic filarial infections. To further our understanding of the host-parasite interaction, we investigated T-cell stimulation by purified filarial recombinant antigens in peripheral blood mononuclear cells derived from filarial-infected individuals. One of a subset of cloned Brugia malayi antigens involved in the humoral immune response to filarial infection was found to be a T-cell-stimulating antigen. The fusion protein encoded by clone lambda Bm19 induced proliferation of human T cells in a parasite-specific, antigen dose-dependent manner. The deduced amino acid sequence from this cloned region revealed 4 predicted T-cell recognition sites. The lambda Bm19 DNA sequence hybridizes to a 3-kb transcript, and in situ mRNA hybridization analyses of the adult female worm demonstrated that this gene is expressed in developing uterine microfilariae. The native parasite protein is present in several developmental stages since clone lambda Bm19 was initially identified with antiserum directed against the infective larval stage; this protein is therefore a potential target for the host's immune system.

Adult↗
PubMed1989

Tropical pulmonary eosinophilia: analysis of antifilarial antibody localized to the lung.

Acute tropical pulmonary eosinophilia (TPE) is characterized by wheezing, pulmonary infiltrates, marked peripheral blood eosinophilia, and very high serum levels of filaria-specific antibodies. To evaluate the amount and character of the filaria-specific antibodies in the lungs in this disorder, bronchoalveolar lavage was carried out in individuals with acute TPE, in normal subjects, and in patients with elephantiasis or asthma. Striking elevations of total IgE were found in the lower respiratory tract epithelial lining fluid (ELF) of patients with TPE along with high levels of filarial-specific IgG, IgM, and IgE. When patients with acute TPE were treated with diethylcarbamazine and evaluated again 6-14 d later, there was marked reduction in ELF parasite-specific IgG and IgE, which paralleled a rapid clinical response. Immunoblot comparison of the antigen recognition patterns of ELF and serum antibodies demonstrated a general similarity in parasite antigens recognized, but the lung IgE and IgG antibodies appeared to recognize only a certain subset of the parasite antigens recognized by serum antibodies. Thus, a profound antibody response to filarial infection is found in the lungs of patients with TPE, suggesting that these filaria-specific antibodies play an important role in the pathogenesis of this disorder.

Acute Disease↗
PubMed1988

Diethylcarbamazine prophylaxis for human loiasis. Results of a double-blind study.

To determine whether infection with Loa loa could be prevented in temporary residents of endemic areas, we conducted a randomized, double-blind, placebo-controlled trial of diethylcarbamazine as a chemoprophylactic agent. Diethylcarbamazine (300 mg) or placebo was taken orally once a week by Peace Corps volunteers serving in Gabon, Cameroon, and the Central African Republic. The participants were assessed clinically and with serologic and parasitologic testing before and yearly during their two years of service. One hundred one persons satisfactorily completed the study. In Gabon (where exposure to the parasite was heaviest), 6 of 20 volunteers (30 percent) in the placebo group had clinical disease, as compared with none of 16 (0 percent) in the diethylcarbamazine-treated group (P less than 0.02). Of those taking placebo, 10 of 20 (50 percent) became seropositive for antifilarial IgG antibody, as compared with 2 of 16 (12 percent) in the drug-treated group (P less than 0.02). Exposure to the parasite appeared to be much lower among the 65 Peace Corps volunteers in Cameroon and the Central African Republic. No volunteer in either group in these countries had overt loiasis; 2 of 40 (5 percent) in the placebo groups in Cameroon and the Central African Republic seroconverted, as compared with none of 25 (0 percent) of those receiving diethylcarbamazine. Occasional nausea was the only symptom significantly associated with the prophylactic drug regimen. We conclude that diethylcarbamazine given orally once weekly can be an effective, acceptable chemoprophylactic agent to prevent loiasis in temporary residents of regions of Africa where Loa loa is endemic.

Adult↗