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T M Foy

Publications and source records attributed to T M Foy.

26 records · Page 2Linked to original sources
PubMed1993

In vivo CD40-gp39 interactions are essential for thymus-dependent humoral immunity. II. Prolonged suppression of the humoral immune response by an antibody to the ligand for CD40, gp39.

The ligand for CD40 has been recently identified as a 39-kd protein, gp39, expressed on the surface of activated CD4+ T helper cells (Th). In vitro, soluble CD40 and anti-gp39 have been shown to block the ability of Th to activate B cells, suggesting that gp39-CD40 interactions are important to T cell-dependent B cell activation. Here it is shown that in vivo administration of anti-gp39 dramatically reduced both primary and secondary humoral immune responses to erythrocytes and soluble protein antigens without altering responses to the T-independent type II antigen, trinitrophenyl-Ficoll. Treatment of mice for 4 d with anti-gp39 inhibited the anti-sheep red blood cell (SRBC) response for at least 3 wk and inhibited the expression of all immunoglobulin isotypes in secondary responses to the protein antigen, keyhole limpet hemocyanin. To examine the direct effect of anti-gp39 on Th function, SRBC-immune Th cells from anti-gp39-treated mice were adoptively transferred and shown to be fully capable of providing help. These results suggest that anti-gp39 treatment does not cause Th deletion or anergy. Anti-gp39 may mediate its profound immunosuppressive effects on humoral immunity by blocking gp39-CD40 interactions. Moreover, these studies establish gp39-CD40 as an important receptor-ligand pair for the targeting of therapeutic antibodies to control thymus-dependent humoral responses.

Animals↗
PubMed1993

Prevention of collagen-induced arthritis with an antibody to gp39, the ligand for CD40.

The ligand for the CD40 antigen is a 39-kilodalton protein, gp39, expressed on the surface of activated CD4+ T cells and is essential for thymus-dependent humoral immunity. The role of gp39-CD40 interactions in autoimmune disease was investigated in vivo with the use of an antibody that blocks their interactions (anti-gp39). Arthritis induced in mice by immunization with type II collagen was inhibited by anti-gp39. Anti-gp39 blocked the development of joint inflammation, serum antibody titers to collagen, the infiltration of inflammatory cells into the subsynovial tissue, and the erosion of cartilage and bone. Thus, interference with gp39-CD40 interactions may have therapeutic potential in the treatment of autoimmune disease.

Animals↗
PubMed1993

Switching capacity of Fc epsilon RII-positive and -negative murine B cells.

In previous studies, our laboratory demonstrated the utility of the low affinity IgE Fc receptor (Fc epsilon RII) in delineating a number of murine B cell subsets. In the spleen, the Fc epsilon RII is expressed on mature conventional B cells but is absent on marginal zone B cells. In the peritoneal cavity, the receptor is present on all conventional B cells, but is not expressed on fresh peritoneal Ly1/sister B cells. The studies in this report compared the ability of these B cell populations to isotype switch. Using a lipopolysaccharide (LPS)- and interleukin (IL)-4-driven system, sort-purified Fc epsilon RII-positive and -negative B cells from peritoneum and spleen were tested for switching to IgG1, IgE, and IgA. The results demonstrated that regardless of their source, Fc epsilon RII+ B cells produced significant levels of IgG1 and IgE. Similar results were obtained with Fc epsilon RII- (marginal zone) B cells obtained from spleen. In contrast, Fc epsilon RII- (Ly1/sister) peritoneal B cells were found to produce IgG1 and IgA, but were incapable of secreting significant levels of IgE. Further studies tested for LPS and IL-4-induced expression of Fc epsilon RII and Thy1 on the various B cell populations. These experiments demonstrated the induction of the Fc epsilon RII on all B cells, regardless of their initial resting levels. Additionally, Thy1 was found to be induced only on those B cell subsets capable of producing IgE. Taken together, the results demonstrate a correlation between IgE secretion and Thy1 expression, and no apparent correlation between the presence of the Fc epsilon RII and isotype commitment.

Animals↗
PubMed1992

Ontogeny and distribution of the murine B cell Fc gamma RII.

The distribution and expression of the IgG FcRII (Fc gamma RII) on normal murine B cells was examined. Using multicolor flow cytometry, spleens from neonatal mice of increasing age and adult bone marrow were analyzed for expression of the Fc gamma RII. In addition, B cells from peripheral lymphoid organs, as well as panel of B cell tumors, were tested. The results demonstrate that the Fc gamma RII is expressed on all pre-B cells and immature B cells in the neonatal spleen and adult bone marrow, on all mature B cells in peripheral lymphoid organs, and on switched B cells in Peyer's patches. Furthermore, the Fc gamma RII was found to be present on B cell tumors representative of all stages of B cell maturation and differentiation. Taken together, the results indicate that Fc gamma RII is expressed during the entire lifetime of the B cell. In addition, examination of spleen cells from neonatal mice revealed a large number of pre-B cells, phenotypically defined as B220+, IgM-. These pre-B cells were present at birth, peaked in number between 2 and 3 wk of age, and became a minor population by day 30. Further phenotypic analysis of these cells demonstrated the expression of the BLA-1 and BP-1 Ag, and the lack of T cell and NK cell markers, thus confirming their assignment to the B cell lineage. Finally, the Fc gamma RII present on these pre-B cells was shown to be functional, by virtue of its ability to bind aggregated IgG.

Animals↗
PubMedDate not supplied

Blockade of CD40-CD154 interferes with human T cell engraftment in scid mice.

Antibodies to the ligand for CD40 (CD154) have been shown to exert profound effects on the development of cell-mediated immune responses in mice. The present study shows that an antibody to human CD154 (hCD40L) inhibits in vivo Tetanus toxoid (TT) specific secondary antibody responses in hu-PBL-scid mice, as well as the expansion of xenoreactive human T cells in the scid mice. A possible cause for the reduced expansion of xenoreactive, human T cells, was the decreased expression of murine B7.1 and B7.2 caused by the administration of anti-hCD40L. Therefore, it may be that defective maturation of murine antigen-presenting cells impeded the priming and expansion of human xenoreactive T cells.

Adult↗