Chediak-Higashi syndrome natural killer cells: a protein kinase C defective activation/regulation defect?
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Biomedical subjects
Publications and source records attributed to E Sabino.
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Infections are major cause of illness and death amongst elderly people. Peripheral blood CD8+ T lymphocytes -which play a crucial role in host defence against viral infections-. are divided in subsets based upon the expression of several cell and activation markers. Since in senescence changes in peripheral blood CD8+ T lymphocyte compartment have been described, studies were performed to determine whether in aging there are variations in the peripheral blood CD8+CD38+, CD8+CD57+, CD8+HLA-DR+, CD8+CD45RA+ and CD8+CD45RO+ cell subset. A decrease in the CD8+CD45RA+ lymphocytes was observed, indicating that variations in the CD8+ compartment can take place with ageing.
OBJECTIVE: To determine whether the HIV-1 genomes that grow out in vitro from peripheral blood mononuclear cells (PBMC) better represent the in vivo quasi-species present in plasma or PBMC. RESULTS: For one patient (9606), PBMC culture represented more accurately the plasma rather than the in vivo PBMC quasi-species distribution, because a large number of tat-defective proviruses present in PBMC in vivo were not detected in plasma nor in the PBMC cultures. For a second patient (9605), PBMC culture was representative of both in vivo PBMC and plasma tat sequences, but selection of C2-V3 env sequences was observed in PBMC cultures compared with sequences present in both plasma and PBMC in vivo. This selection consisted of the absence in vitro of genomes with certain amino-acid substitutions at or near conserved glycosylation sites of the C2 region at positions 276 and 289. Site 276 has been reported to be important for viral infectivity, and these substitutions may therefore have affected infectivity. In the third patient (10095), selection of both tat and C2-V3 sequences was observed in culture as compared to plasma and PBMC in vivo. In contrast to the first two patients, this third patient contained V3 sequences in vivo that were predicted to impart syncytium induction and enhanced replication capacity. It was these sequences that grew out preferentially in vitro. CONCLUSION: This study suggests that short-term PBMC culture is representative of HIV-1 genomes present in PBMC and plasma in vivo to the degree that they are infectious.
The first exon of tat was sequenced from 23 provirus genomes randomly amplified directly from an HIV-1-infected individual's peripheral blood. Twelve of the 23 sequences constituted a distinct subset of the quasi-species detected. This subset had in common two inactivating mutations in the tat gene. In addition, two of these defective genomes each had a unique mutation. This is the second instance of a defective early gene being present in a high percentage of the proviruses present in the PBMCs of an HIV-1-infected individual, (the first reported by Martins LP et al.: J Virol 1991;65:4502-4507), and suggests that genomes defective in an early gene can participate in the infectious spread of HIV-1 in vivo.
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The T V alpha and V beta cell specificities repertoire usage in aging subjects was studied by the use of seven different monoclonal antibodies specific for defined regions of the T cell receptor (TCR). Except for the V beta 8 subfamily, no differences were observed in the frequency of T cells bearing selected V alpha beta epitopes, between old and control subjects.