Biomedical subjects

B R Yacyshyn

Publications and source records attributed to B R Yacyshyn.

21 records · Page 2Linked to original sources

PubMed1993

Activated CD19+ B cell lamina propria lymphocytes in ulcerative colitis.

Although isotype differences in lamina propria lymphocyte (LPL) immunoglobulin production has been recognized between normal, ulcerative colitis (UC) and Crohn's patients, differences in B cell activation between these conditions has not been described. Using flow cytometry, we studied B cell LPL activation using the CD71 (transferrin receptor), CD25 (interleukin-2 receptor) and 4F2 (early B and T cell activation marker) monoclonal antibodies. CD19+ B cells from patients with UC had relatively increased expression of CD71, CD25 and 4F2 compared with patients with Crohn's disease or normal mucosa. This finding corresponds to an increased proportion of transitional (activated) B cells as defined by the co-expression of CD45RA and CD45RO found in UC LPL compared with normal or Crohn's patient LPL. Such data may identify an important link between the cellular state of activation of UC LPL B cells and the differences in immunoglobulin production between the inflammatory bowel diseases and normal intestine. Such findings may have further diagnostic or pathophysiologic importance in the study of these diseases. This work also provides further support for the CD45 transition of CD19 B cells from the high to low molecular weight isoform.

Antibodies, Monoclonal↗

PubMed1993

Expression of CD45RO on circulating CD19+ B-cells in Crohn's disease.

Crohn's disease is an immunoregulatory disorder of the intestine that can be associated with systemic manifestations. This study analysed B-cell differentiation antigens to identify B-cell subpopulations unique to patients with Crohn's disease. CD45 isoform expression was used as an indicator of B-cell differentiation stage. This work shows that B-cells in blood and gut of patients with Crohn's disease are at an advanced stage of differentiation based on their unusual presentation of transitional (RA+ RO+) and late stage (RO+)CD45 isoforms on lamina propria lymphocytes, whereas normal intestinal lamina propria lymphocytes B-cells express primarily CD45RA. Crohn's disease patients had heightened expression of the CD45RO isoform on CD19+ lamina propria lymphocytes, and was found in a statistically significant proportion of Crohn's peripheral blood mononuclear cells (PBMC) where CD19+ PBMC had an expression pattern affecting an unexpectedly high proportion of these differentiated or late stage CD45RO+ B-cells. The expression of CD45RO varied greatly among CD19+ PBMC from patients with Crohn's disease, so multiple regression analysis was performed between these CD45 isoforms and several clinical parameters. After grouping high and low CD45RO expression on CD19+ B-cells, a significant statistical difference was found between high Crohn's disease activity index (CDAI) and low CDAI Crohn's disease patients respectively.

Antigens, CD↗

PubMed1991

Beta 1 integrin (CD29) expression on human postnatal T cell subsets defined by selective CD45 isoform expression.

The integrin beta 1 (CD29) is a marker for total very late activation Ag integrins on cells, and exhibits considerable fluctuation in cell surface density at various stages of T cell development. We have analyzed beta 1 integrin expression on subsets of human thymus, and on T cells from healthy babies and children, in comparison to healthy adults aged 26 to 75. T cells from adult peripheral blood include a CD29-, a CD29lo, and a CD29hi set. Compared with adults, PBMC T cells from children have reduced numbers of both CD29lo and CD29hi subsets but equivalent numbers of CD29- T cells. The number of CD29hi T cells increases gradually with age, achieving adult levels only at about 26 yr of age; in aged adults (69 to 75 yr), nearly all T cells have a CD29hi phenotype. Most thymocytes and cord blood T cells, in contrast, have a single peak of CD29 staining that is intermediate to the two peaks seen in adults. Multi-negative progenitor and CD45RO- thymocytes (presumptive thymic generative line-age) are 98% CD29hi. Progenitor thymocytes and adult PBMC T cells express equivalent amounts of beta 1 and alpha 4, but progenitors are alpha 5hi, whereas PBMC T cells are alpha 5lo. T cells from children have reduced beta 1hi and alpha 5lo, but nearly comparable numbers of alpha 4hi. This suggests that the major very late activation Ag integrins during childhood may be alpha 5 beta 1 and alpha 4 complexed with an alternate beta chain. In children, the majority of CD29hi cells are also CD45RAhi, in contrast to the pattern in adults, in whom the majority of CD29hi T cells are CD45RA-. This suggests that in children, the main defense against infection may reside in the CD29hi45RAhi T cells, which have not yet made the transition to CD45RO and to bona fide memory status. The proliferative response to tetanus toxoid of 4- to 6-mo-old babies correlates with the number of CD29hi45RAhi T cells, suggesting that it derives at least in part from cells that do not express a "memory" phenotype. These observations show a pattern of alternating high and low density CD29 during T cell development, which is consistent with the idea that CD29 is a marker for functionally defined T cell sets. Analysis of the CD29 expression of CD29hi thymocytes developing in vitro supports this view. We suggest that the intensity of CD29 expression on a T cell varies, dependent upon the microenvironmental interactions required by a differentiating T cell.

Adolescent↗