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Biomedical subjects

G Kingsley

Publications and source records attributed to G Kingsley.

47 records · Page 3Linked to original sources
PubMed1988

The preferential accumulation of helper-inducer T lymphocytes in inflammatory lesions: evidence for regulation by selective endothelial and homotypic adhesion.

The mechanisms which lead to the accumulation of T lymphocytes into inflammatory lesions are not clearly understood. We have previously shown that synovial CD4 T lymphocytes are mostly CDw29+UCHL1+ (helper-inducer cells) and very few carry the CD45R antigen which identifies the suppressor-inducer subset. Synovial CD8+ cells are also CDw29+UCHL1+CD45R-. In the present study, lymphocytes from pleural and peritoneal inflammatory infiltrates were shown to have a similar phenotypic pattern. Furthermore, it was demonstrated that the CDw29+UCHL1+ subset had a greater ability than CD45R+ cells to adhere to endothelial cells and to form homotypic clusters. Differential surface expression of LFA-1 on the two subsets was also shown, but this could not account for the demonstrated adhesion differences. Differences in adhesion between CDw29+/UCHL1+ and CD45R+ cells may explain the preferential accumulation of CDw29+/UCHL1+ cells in inflammatory infiltrates and underlie some of the functional differences between cells taken from sites of chronic inflammation and those from peripheral blood.

Antigens, Differentiation↗
PubMed1988

Abnormal helper-inducer/suppressor-inducer T-cell subset distribution and T-cell activation status are common to all types of chronic synovitis.

We have previously shown that rheumatoid synovial T cells are virtually all helper-inducer (CD4+4B4+UCHL1+) rather than suppressor-inducer (CD4+2H4+) cells. CD8 cells were also largely 4B4+. In addition, the majority of T cells were HLA-DR+. To investigate whether these findings were specific for rheumatoid disease, we studied the prevalence of these markers in a variety of chronic inflammatory arthropathies such as ankylosing spondylitis, Reiter's syndrome, and psoriatic arthritis. Again, almost 90% of the T cells were 4B4+UCHL1+ and only 11% were 2H4+; 50% expressed the HLA DR antigen. Thus this phenotypic distribution represents a final common pathway of chronic synovitis and may help to explain the immunopathology of the lesion.

HLA-D Antigens↗
PubMed1988

Correlation of immunoregulatory function with cell phenotype in cord blood lymphocytes.

The strong suppressor activity of cord T lymphocytes contrasts markedly with their mainly CD4 (helper) rather than CD8 (suppressor) phenotype. We studied the phenotype of cord CD3, CD4 and CD8 cells compared to adult cells using the monoclonal antibodies, 2H4, 4B4, and UCHL1. Almost all cord CD4 lymphocytes carried the suppressor-inducer marker 2H4, whereas 4B4+ UCHL1+ helper-inducer cells were virtually absent; CD8 cord cells were also of the 2H4+ 4B4- UCHL1- phenotype. In contrast in adult peripheral blood, half of the T cells, whether CD4 or CD8, were 2H4+ and half 4B4/UCHL1+. The suppressor-inducer phenotype of cord T cells was shown, in parallel functional experiments, to correlate with their enhanced proliferation to lectin and poor production of immunoglobulin and with the ability of cord mononuclear cells to suppress proliferation and immunoglobulin production by adult cells in co-culture experiments. These results indicate that the major imbalance in the cord CD4 subset in favour of 2H4 cells can explain many of the functional differences from adult cells. However, involvement of other cell types, in particular of the monocyte lineage, is necessary to explain other properties of immunocompetent cord cells.

Adult↗
PubMed1987

Abnormal distribution of the helper-inducer and suppressor-inducer T-lymphocyte subsets in the rheumatoid joint.

T lymphocytes can be divided into two main phenotypic populations, CD4 and CD8. These can be further subdivided into 2H4, 4B4, or UCHL1 subsets by appropriate monoclonal antibodies. We have investigated these subsets in the synovial fluid of patients with rheumatoid arthritis and have found (i) a virtual absence of CD4+ 2H4+ and the marked reduction of CD8+ 2H4+ T cells; (ii) a marked increase of CD4+ 4B4+ and CD8+ 4B4+ T cells; and (iii) a marked increase of CD4+ UCHL1+ and CD8+ UCHL1+ T cells compared with peripheral blood. Although the functions of the CD8 subsets are not known, the virtual absence of CD4+ 2H4+ suppressor-inducer T cells and the marked increase of CD4+ 4B4+ helper-inducer T cells and of CD4+ UCHL1+ memory T cells may help to explain the many known functional immunological properties of synovial T cells.

Antibodies, Monoclonal↗
PubMed1987

Expression of HLA-DR, DQ and DP antigens and interleukin-2 receptor on synovial fluid T lymphocyte subsets in rheumatoid arthritis: evidence for "frustrated" activation.

Synovial fluid and peripheral blood T lymphocytes were examined from 10 patients with rheumatoid arthritis and 2 controls. T lymphocytes from inflammatory fluids were activated as shown by their increased size and expression of class II MHC antigens. Of the T cells, 60% were DR positive, 19% DP positive and 29% DQ positive. More Leu 2a than Leu 3a cells were HLA-DR positive. In contrast, few T cells expressed Tac. We conclude that T cell activation is taking place but is incomplete or "frustrated".

Adult↗
PubMedDate not supplied

Joint damage and disability in rheumatoid arthritis: an updated systematic review.

Joint damage and disability in rheumatoid arthritis (RA) both increase with disease duration but the nature of their relationship is uncertain. This review updates knowledge of the progression and inter-relationship of joint damage and disability in treated RA and provides a synopsis of the main predictive factors for damage and disability. In early RA 39-73% of patients develop one or more erosions in their hands and wrists by 5 years. In established RA the average annual increase in radiological damage scores is 1.9% maximal damage. After 20 years RA patients have on average 43% of maximum possible damage. These data suggests that joint damage progresses constantly over the first 20 years of RA. The average annual increase in HAQ scores is 0.033 per year (1% of possible maximum disability). In the first years of disease there is a "J-shaped" curve with an initial fall in HAQ scores followed by an increase over the next four years. In cross-sectional studies there is either no correlation or a weak correlation between damage and disability in early RA; this absence of correlation is explained by the "J-shaped" curve of disability with disease duration in early RA. As disease duration increases the correlation between damage and disability becomes more obvious; 9 studies show correlation coefficients between 0.31 and 0.75. The most predictive factors of damage and disability are rheumatoid factor status and disease activity. The validity of our conclusions are limited by the potential indirect link between small joint damage and disability, with large joint damage being a more important predictor, and the presence of ceiling effects on X-rays. In conclusion, joint damage accounts for a substantial proportion of the disability associated with the disease.

Adult↗
PubMedDate not supplied

Class II MHC binding peptides: a feasible treatment for arthritis?

The association of rheumatoid arthritis with the MHC class II alleles HLA DR4 and HLA DR1 may be due to their capacity to present an arthritogenic peptide to T cells, thus inducing the disease. Interfering with this presentation using a competitor peptide would inhibit the disease and such therapy has been effective in animal models. These studies, and the possibility of transferring the therapy to humans, will be reviewed.

Animals↗
PubMedDate not supplied

Joint destruction in rheumatoid arthritis: biological bases.

The pathogenesis of rheumatoid arthritis (RA) can be explained through two main hypotheses: macrophage-fibroblast and macrophage-T cell interactions. The interplay between the various populations is influenced by a strong genetic component, which determines the severity of the disease in some cohorts of patients attending referral centers. The key question of the nature of the antigen(s) driving joint inflammation still remains unsolved. Exogenous antigens such as viruses or bacteria have long been searched for in the synovial fluids as well as in tissues, but convincing evidence of their pathogenic role are lacking. Data have been accumulated on the possible role of autoantigens, such as the spliceosomes, filaggrin, calpastatin, type II collagens, or other endogenous peptides, but no definite role regarding their potential contribution to the activation of T cells has been established. Once the process starts, a progressive recruitment of inflammatory T cells and macrophages into the joints occurs through a complex series of adhesion and migratory events. The key driving steps leading to synovial inflammation and cartilage destruction, along with the potential contribution of some key molecules, have been described, thus opening possible perspectives for a therapeutic approach.

Antigen-Presenting Cells↗