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Biomedical subjects

E Carrow

Publications and source records attributed to E Carrow.

9 recordsLinked to original sources
PubMed1997

Antigen-driven C-C chemokine-mediated HIV-1 suppression by CD4(+) T cells from exposed uninfected individuals expressing the wild-type CCR-5 allele.

Despite repeated exposure to HIV-1, certain individuals remain persistently uninfected. Such exposed uninfected (EU) people show evidence of HIV-1-specific T cell immunity and, in rare cases, selective resistance to infection by macrophage-tropic strains of HIV-1. The latter has been associated with a 32-base pair deletion in the C-C chemokine receptor gene CCR-5, the major coreceptor of macrophage-tropic strains of HIV-1. We have undertaken an analysis of the HIV-specific T cell responses in 12 EU individuals who were either homozygous for the wild-type CCR-5 allele or heterozygous for the deletion allele (CCR-5Delta32). We have found evidence of an oligoclonal T cell response mediated by helper T cells specific for a conserved region of the HIV-1 envelope. These cells produce very high levels of C-C chemokines when stimulated by the specific antigen and suppress selectively the replication of macrophage-tropic, but not T cell-tropic, strains of HIV-1. These chemokine-producing helper cells may be part of a protective immune response that could be potentially exploited for vaccine development.

Alleles↗
PubMed1996

Role of HLA class I in HIV type 1-induced syncytium formation.

Neutralization of HIV-1 in vitro by anti-HLA class I antibodies suggests that class I molecules are involved in HIV-1 infection. HIV-infected cells can fuse with uninfected cells in a process that leads to the formation of multinucleated syncytia, involving an interaction between host and viral antigens expressed at the cell surfaces. We used a syncytium assay between the 8E5 cell line chronically infected with a pol-defective variant of LAV IIIb, and the CD4-positive cell line MOLT3, to study the role of HLA class I in HIV-1-induced cell fusion. By probing cells with a panel of anti-HLA monoclonal antibodies (MABs) we demonstrated that the fusion process is modulated specifically by C alleles of HLA class I expressed on uninfected cells but not by that on already infected cells. Addition of beta 2-microglobulin to the cocultures resulted in a dose-dependent enhancement in both the number and size of syncytia, whereas exogenous HLA-C-restricted peptides inhibited syncytium formation, implying that only certain conformational states of HLA class I are permissive for syncytium formation. Treatment of cocultures with HLA-Cw4-restricted peptides containing amino acid substitutions in the anchor residues showed that syncytium inhibition was dependent on conventional binding of the peptide inside the groove. The data indicate that HLA class I, in a conformation free of peptide but associated with beta 2-microglobulin, can directly influence virus-induced cell fusion.

Antibodies, Monoclonal↗
PubMed1996

HIV-1-specific immunity in persistently seronegative individuals at high risk for HIV infection.

A growing number of reports indicates that certain groups of individuals who almost certainly have been exposed to human immunodeficiency virus (HIV), yet continue to exhibit no signs or symptoms of infection, often have subtle evidence of specific immunity. We studied such a high-risk (HR) cohort of persistently seronegative individuals with histories of long-term sexual exposure to an HIV-infected partner to look for evidence of both humoral and cellular immunity that might have been induced by exposure to the virus. Twenty-three heterosexual and four homosexual monogamous couples with discordant HIV status were included in the study. Twelve of the HR partners were studied for in vitro stimulation of peripheral blood mononuclear cells (PBMC) by HIV envelope-derived peptides. All 12 responded overwhelmingly to a peptide containing the fifth conserved region of gp120. By generating and cloning T cell lines specific for this peptide, we concluded that in these individuals the T cell response to the envelope is mainly focused on the carboxy-terminus region of gp120 and is characterized by an oligoclonal expansion of CD4+ T cells expressing the same TCR Eighteen HR partners and 37 HIV-1 seropositive subjects were tested for the presence of anti-CD4 antibodies (anti-CD4 Abs) using a recombinant CD4-based enzyme-linked immunosorbent assay (ELISA). Anti-CD4 Abs were detected in eight of the HR partners (six confirmed by Western blot) and in nine of the HIV-1 seropositive subjects (eight confirmed by Western blot). Results from binding competition assays with a panel of monoclonal anti-CD4 Abs suggested that the anti-CD4 Abs detected in the HR partners are directed toward epitopes that are induced by gp120 binding. Twenty-seven of the HR partners were tested for the presence of antibodies that cross-react with HLA class I and gp120 (anti-HLA Abs). Anti-HLA Abs were detected in 16 of the HR partner sera and in 4/94 sera from a control population of normal healthy blood donors. Taken together, the results suggest that in some individuals with a history of long-term exposure to HIV, specific immunity may develop in the absence of overt infection. The common trigger for these responses is gp120.

Antibodies↗
PubMed1992

Variable infections with and serologic responses of rabbits to five different HIV-1 strains, including one neural tissue isolate.

The infectivity of different strains of HIV-1 in rabbits was investigated. The HIV-1RF and HIV-1MN inocula induced anti-envelope antibodies detectable by Western blot, and in the case of HIV-1RF, these antibodies were also detectable by ELISA. The peripheral blood lymphocytes (PBL) and lymph nodes from rabbits inoculated with HIV-1IIIB, HIV-1MN and HIV-1Z3, were positive for virus by culture and by polymerase chain reaction (PCR). HIV-1BRVA, originally isolated from a patient with AIDS dementia, infected the brain of the inoculated rabbit, as indicated by both virus culture and PCR. In this case PCR was positive using four different primer pairs. Throughout the study, rabbits showed no clinical signs of HIV-1 infection and no remarkable histopathology was observed in the tissues examined. The apparent differences in infectivity and tissue tropism of the five HIV-1 strains demonstrated here provide additional evidence that the rabbit may serve as a useful model for studying HIV-1 infection and pathogenesis.

Animals↗
PubMed1987

Soy- and shrimp-specific IgE responses in orally and intraperitoneally immunized mice.

Female C3H/HeJ mice were immunized parenterally and/or intragastrically with two important food allergens, soy and shrimp. Although both preparations elicited specific IgE production when administered intraperitoneally, anti-shrimp titers were consistently higher. Soy or shrimp administration, i.g. with Pertussis adjuvant (intraperitoneally or intragastrically) did not induce detectable reaginic antibody. Animals treated with soy intragastrically were unable to produce a soy-specific IgE response upon intraperitoneal immunization. The combination of soy and Pertussis (intragastric) did, however, abrogate this tolerizing effect on IgE synthesis. In contrast to soy, the shrimp antigens (intragastric) did not act as tolerogens and were found to enhance subsequent reaginic responses produced by intraperitoneal immunization. These results are considered with respect to mechanisms operative in food allergy.

Adjuvants, Immunologic↗
PubMed1973

Dyslexia.

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Auditory Perception↗