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Biomedical subjects

M D Cooper

Publications and source records attributed to M D Cooper.

At least 181 records · Page 10Linked to original sources

Relationship of changes in condition score to cow health in Holsteins.

The relationship of body condition score with disease occurrence was examined in 561 cows in nine herds. Cows were body condition scored on a five-point scale (1 = thin, 5 = obese) every 2 wk from drying off until 150 d in milk. Cows scored between 3- and 3+ were considered to be in average or good condition. Cows scored less than or equal to 2+ were considered to be underconditioned, whereas those scored greater than or equal to 4- were considered to be overconditioned. Relationships of health and condition score were examined using multiple logistic regression for dichotomous outcomes (e.g., diseased or healthy). Cows that developed dystocia or were culled lost more condition during the dry period than those that did not develop dystocia or were not culled. Cows overconditioned at drying off were more likely to develop cystic ovarian disease and reproductive problems. Cows underconditioned or overconditioned at drying off were more prone to foot problems after calving. Cows overconditioned at 30 d postpartum were more likely to have metritis.

Animals↗

T cell differentiation in birds.

Avian T cell development has been traced using monoclonal antibodies specific for chicken T cell surface differentiation antigens. The basic antigen recognition molecules, differentiation pathways, and functional capabilities defined for T cells in mammals are highly conserved in birds. Novel features of T cell development are also revealed. These include the generation of a third T cell sublineage that expresses a different receptor isotype (TCR3) and a novel lineage of cytoplasmic CD3+ lymphoid cells (TCR0 cells). In contrast to the TCR0 cell lineage, the sublines of T cells bearing the three TCR isotypes are all generated exclusively within the thymus.

Animals↗

Regulated expression of cell surface antigens during B cell development.

The progression of lymphocytes along the B cell developmental pathway is marked by the regulated appearance and disappearance of a variety of cell surface markers including immunoglobulin. In this review, several of these antigens are discussed in the context of their possible functions during normal B cell differentiation.

Animals↗

Characterization of suppressor T cells for antibody production by chicken spleen cells. I. Antigen-induced suppressor cells are CT8+, TcR1+ (gamma delta) T cells.

Suppressor activity of chicken T cells has been previously defined in an in vitro assay of the secondary response of spleen cells to sheep erythrocytes. We have used this assay to examine the phenotype of the T-cell subpopulation(s) that is responsible for this activity. The suppressive effect was alleviated by removal of the TcR1+ (gamma delta) and CD8+ subpopulations, but was unaffected by the removal of the TcR2+ (alpha beta) and CD4+ cells. The addition of a histamine type 2 (H2) receptor antagonist, cimetidine, enhanced the antibody response in the presence of the suppressor cells. The data indicate that one type of T cells with suppressor capability expresses TcR1 and the CD8 accessory molecule, and that these cells may be influenced via H2 receptors.

Animals↗

Human IL-7: a novel T cell growth factor.

IL-7 is a hemopoietic growth factor that induces the proliferation of early B lineage cells. In the course of studies to determine its effect on human bone marrow cells, we noted a marked outgrowth of mature T cells. When T cells from the circulation were cultured with IL-7, a dose-dependent proliferative response was observed. The target cells included both the CD4+ and CD8+ subpopulations of T cells, but the memory T cells (CD45R-) were better responders than unprimed T cells (CD45R+). IL-7 induced the expression of receptors for IL-2 and transferrin and higher levels of the 4F2 activation Ag. Although T cell responses to suboptimal concentrations of IL-7 were enhanced by the addition of IL-2, the proliferative response to IL-7 was not inhibited by neutralizing antibody to the IL-2R (Tac), nor was IL-2 secretion detected in this response. This response pattern of mature T cells suggests an important role for IL-7 in normal T cell physiology in humans.

Adult↗

The early B lineage antigen BP-1 and the transformation-associated antigen 6C3 are on the same molecule.

Biochemical similarities and cellular distribution patterns of the early B lineage-specific BP-1 alloantigen and the B lineage transformation-associated 6C3 Ag prompted this comparative study of the reactivities of the BP-1 and 6C3 mAb. Both Ag were found to be expressed on the same cells in normal tissues, and on the same cell lines when a large panel was analyzed. The Ag are both phosphorylated and have identical m.w., which may vary in different cell types because of differences in glycosylation. Immunoprecipitation of pre-B cell lysates with the BP-1 antibody removed the 6C3-reactive molecules and vice versa. However, the 6C3 antibody did not inhibit binding of the BP-1 antibody to viable cells and, in fact, enhanced immunofluorescence staining was observed when both antibodies were added together. These results indicate that the BP-1 and 6C3 antibodies react with different epitopes on the same molecule that is expressed in relatively low levels on normal early B lineage cells, and in relatively high levels on most neoplastic pre-B cells, pre-B cells in long term bone marrow cultures and certain stromal cell lines.

Animals↗

Epstein-Barr virus preferentially induces proliferation of primed B cells.

EBV can induce human B cells to proliferate, differentiate, and undergo transformation into continuously growing lymphoblastoid cell lines. The EBV responsiveness appears to be confined to a very limited subpopulation of B cells, the nature of which is still unclear. In these studies, we sorted tonsillar B cells on the basis of their expression of the early surface activation Ag, Bac-1, and compared their proliferative responses to EBV. Bac-1+ cells responded to EBV with a relatively high level of DNA synthesis, whereas the Bac-1- cells did not. Both large and small Bac-1+ cells were responsive to EBV and the responsiveness was unrelated to the level of Bac-1 immunofluorescence intensity. Bac-1+ cells were relatively enriched for surface IgM and IgD expression. When the Bac-1- population was enriched for IgM+ cells, the proliferative response was still significantly lower than that of the Bac-1+ population. B cells acquire the ability to bind IgM relatively late after activation, and this feature did not distinguish the EBV-responsive B cells. The results suggest B cells become responsive to EBV after an early activation signal.

Adult↗

Analysis of the first two waves of thymus homing stem cells and their T cell progeny in chick-quail chimeras.

Chick-quail chimeras were used to study precursor/progeny relationships of hemopoietic stem cells (SC) that enter the embryonic thymus in waves to give rise sequentially to the TCR-1+, TCR-2+, and TCR-3+ lineages of T cells. The first wave of SC and their progeny were examined by grafting thymus from 9-d chick embryos (E9) into E3 quails. mAbs specific for chick T cell antigens were used to trace the development of T cells in the recipients. All three lineages of TCR-bearing cells were generated from the first wave of SC. The cortico-medullary transit time was several day shorter for the TCR-1 subpopulation than for the TCR-2 subpopulation, and the peripheral seeding of TCR-2 cells also occurred later in development. The duration of thymocyte production from the first wave of SC that entered the thymus was approximately 3 wk, during which gradual cortical to medullary replacement by second wave SC progeny occurred. When the latter was examined, after transplantation of E7 quail thymus into E3 chick embryos, a sequential generation pattern for the TCR-1 and TCR-2 cell progeny was not evident. Finally, recirculation of T cells to the thymus medulla was defined in this avian model.

Age Factors↗

Tissue localization and CD8 accessory molecule expression of T gamma delta cells in humans.

In this study, we used TCR isotype-specific antibodies to examine the frequency, phenotype, and histologic localization pattern of T gamma delta cells in humans. The TCR delta 1+ cells comprised an average of 15% of the splenic CD3+ cells and 7% of circulating T cells. The T gamma delta cells in these human tissues, like their avian counterparts, were often not "double-negative" for the CD4 and CD8 accessory molecules. Approximately 50% of the splenic delta+ cells expressed CD8, and 30% of the delta+ cells in blood were CD8+. T cells of both gamma delta and alpha beta TCR isotypes were exceedingly rare in the skin. The T gamma delta cells exhibited preferential homing to the sinusoidal areas (red pulp) of the spleen and into the epithelial layer of the intestine in humans, as had been previously noted in chickens. Although 80% of the T gamma delta cells in the human intestinal mucosa were localized in the epithelial layer, these cells represented only 5 to 10% of all the CD3+ T cells in this microenvironment. We conclude that T gamma delta cells represent a sizeable subpopulation of the T cells in human peripheral tissues. The phylogenetic conservation of the CD8 expression by peripheral T gamma delta cells and of their preferential homing pattern suggests a special role in bodily defense for this T cell subpopulation.

Aged↗

Immunofluorescence analysis of IgA binding by human mononuclear cells in blood and lymphoid tissue.

The nature of IgA-binding cells and their tissue distribution was examined by an indirect immunofluorescence assay with the use of IgA1 and IgA2 paraproteins and fluorochrome- or biotin-labeled F(ab')2 fragments of idiotype-specific antibodies. The frequency of IgA-binding mononuclear cells was approximately 13% in blood and spleen samples but less than 1% in tonsil samples. IgA binding could be visualized by flow immunocytometry on monocyte/macrophages, but not on T and B cells. IgA polymers were bound better than IgA dimers and monomers. Nonhomologous IgA myelomas of both IgA1 and IgA2 subclasses inhibited the IgA-binding to monocytes, whereas aggregated normal serum IgG, IgM paraproteins, and an IgG myeloma did not. IgA binding was relatively insensitive to changes in temperature or cation concentration. IgA-binding monocytes were found in IgA-deficient patients at the same frequency as in normal individuals. The results indicate that monocytes constitutively express class-specific binding sites for both IgA1 and IgA2 molecules.

Agammaglobulinemia↗

Cytoplasmic CD3+ surface CD8+ lymphocytes develop as a thymus-independent lineage in chick-quail chimeras.

We have analyzed the embryonic development of a population of lymphoid cells that express a CD3 antigenic determinant in the cytoplasm but not on the cell surface. Since these cells lack T cell receptor (TcR) molecules, we have provisionally named them TCRO cells. Their development, expansion and distribution was investigated following transplantation of splenic and bursal fragments from chicken embryos into quail embryos. Since quail cells are not recognized by our panel of monoclonal antibodies against chicken TcR1, TcR2, TcR3, CD3, CD4 and CD8 molecules, these antibodies provided reliable markers for donor chick lymphocytes in the tissues of the quail recipients. Transplanted spleen and bursa both generated CD3+ cells, the number of which increased as a function of age. Notably, approximately half of these CD3+ cells expressed surface CD8, but none acquired TcR1 (gamma/delta), TcR2 (alpha/beta) or TcR3 expression. Since TCRO cells normally appear first in the spleen of 8-day chick embryos (E8), their generation in E6 splenic transplants indicated an extrathymic origin. The TCRO cells of chick splenic origin migrated to the spleen, bursa and thymus of the quail recipients. In six of seven chimeras acquiring CT3+ cells in the recipient thymus, these cells were restricted to the medulla and displayed the typical TCRO phenotype: CD3+CD8+TcR1-TcR2-TcR3-. These intrathymic TCRO cells also lacked the CT1 thymocyte antigen. We conclude that the TCRO cells represent a thymus-independent lineage of lymphoid cells that can migrate into a receptive thymus by rarely, if ever, differentiate into conventional T cells.

Animals↗

Individuals with IgA deficiency and common variable immunodeficiency share polymorphisms of major histocompatibility complex class III genes.

IgA deficiency and common variable immunodeficiency are heritable disorders that can occur within the same family. Both immunodeficiencies are characterized by arrests in B-cell differentiation that vary in the extent of the immunoglobulin isotypes involved. A high frequency of major histocompatibility complex supratypes associated with a null allele of the gene encoding the C4A isotype of complement component C4 has been observed in IgA-deficient individuals. In search of a genetic linkage between the two immunodeficiencies, we examined the major histocompatibility complex (MHC) class III genes encoding complement components C2, C4A, and C4B and steroid 21-hydroxylase in addition to the HLA serotypes in individuals with either common variable immunodeficiency or IgA deficiency. Twelve of 19 patients with common variable immunodeficiency (63%, P less than 0.001) and 9 of 16 patients with IgA deficiency (56%, P less than 0.01) had rare C2 alleles and/or C4A and 21-hydroxylase A deletions, whereas these gene features were seen in only 5 of 34 healthy individuals (15%) in the control group. Nine of 11 patients with C4A deletion had an HLA haplotype consistent with the MHC supratype HLA-A1, Cw7, B8, C4AQ0, C4B1, BfS, DR3 previously found to be associated with IgA deficiency. The data support the hypothesis that common variable immunodeficiency and IgA deficiency are related disorders, susceptibility to which is determined by a gene(s) within or near the MHC class III gene region on chromosome 6.

Alleles↗

TCR3: a third T-cell receptor in the chicken.

Avian homologues of mammalian gamma delta and alpha beta T-cell antigen receptors, TCR1 and TCR2, have been identified with monoclonal antibodies. These TCR isotypes are associated with the avian CD3 proteins on the T-cell surface. During chick development, T-cell subpopulations bearing CD3/TCR1 or CD3/TCR2 receptor complexes are generated sequentially in the thymus and seeded to the periphery in the same order. In this study, we used two-color immunofluorescence to identify the subsequent development of a third subpopulation of T cells, provisionally named TCR3. These CD3+ cells, which expressed neither TCR1 nor TCR2, were first detected in the blood 1 week after hatching and increased numerically as a function of age to account for approximately 15% of the circulating T-cell pool in adults. Most (greater than 80%) of the TCR3 cells expressed the CD4 accessory molecule. The relative incidence of the TCR3 subpopulation increased dramatically as a consequence of embryonic treatment with anti-TCR2 antibody and thymectomy after hatching. Two disulfide-linked polypeptides, of Mr 48,000 and 40,000, were associated with the CD3 complex on the TCR3 cells. Examination of the TCR protein backbones and peptide mapping of the TCR chains after partial proteolysis indicated that the TCR3 heterodimer differs from both TCR1 and TCR2. These results suggest the existence of a third class of T-cell receptors in birds.

Animals↗

Light-chain gene expression before heavy-chain gene rearrangement in pre-B cells transformed by Epstein-Barr virus.

Epstein-Barr virus transformation of B-cell-depleted bone marrow cells from human fetuses allowed us to identify novel cell types characterized by the expression of immunoglobulin kappa or lambda light chain without heavy chains. Four kappa-only clones with normal karyotype were obtained and examined for their immunoglobulin gene configurations and expression. All four clones had kappa-chain gene rearrangements at either one or both alleles, but the heavy-chain gene loci in these clones either were in germ-line context or had undergone only D-JH rearrangements (D and JH represent diversity and joining gene segments). All clones contained kappa mRNA of normal size at levels consistent with the protein level, except for one clone that no longer produced kappa protein. No mu mRNA or immunoglobulin heavy-chain molecules were detected in any of the kappa+ clones. The results suggest that the mu heavy-chain protein is not an obligatory prerequisite for light-chain gene rearrangements.

Antibodies, Monoclonal↗

Virgin and memory T cells have different requirements for activation via the CD2 molecule.

T cells can be divided into unprimed virgin (T0) and primed memory (T') subpopulations by their expression of different isoforms of the leukocyte common antigen. We have separated the CD4+ T cells into T0 and T' subpopulations and examined their capacity to respond to activation signals via the CD2 receptor molecule. On stimulation with a mitogenic combination of anti-CD2 antibodies, the T' population was induced to express IL-2 receptor, increased levels of the 4F2 antigen and to proliferate, whereas the response of the T0 populations was reflected solely by a minimal increase in the 4F2 antigen. The addition of IL-2 or monocytes to T0 cells stimulated with anti-CD2 antibodies did not enhance their expression of the IL-2 receptor or proliferation. However, T0 cells stimulated with the triad of anti-CD2 antibodies, monocytes, and IL-2 responded with high levels of IL-2 receptor expression and proliferation. The T0 subpopulation could also be induced to respond when cultured with anti-CD2 antibodies and phorbol myristate acetate. The results suggest that in order to respond to stimulation via the CD2 molecule, virgin T helper cells require additional signals that can be jointly provided by monocytes and IL-2. In contrast, memory T helper cells can be activated via CD2 signal transduction alone.

Antibodies↗

Mu heavy chains can associate with a pseudo-light chain complex (psi L) in human pre-B cell lines.

In pre-B cells, the earliest identifiable stage of B cell differentiation, there is an asynchrony of immunoglobulin chain expression in that mu heavy chains are synthesized in the absence of light chain synthesis. These mu chains largely remain intracellular and are degraded. Here we demonstrate that a fraction of mu chains in human pre-B cell lines can reach the surface in association with three pre-B-specific proteins with relative molecular masses of 22, 18, and 16 kd, which we term collectively the pseudo-light chain complex, psi L. This association generates a multimeric complex, mu 2-psi L. Two of the psi L proteins (22 and 16 kd) are lambda-immunoreactive and form disulfide bonds with mu chains, suggesting that they are closely related to conventional lambda light chains. The 18 kd psi L species is a non-covalently-associated member of the complex. The expression of mu-psi L complexes on the surface of pre-B cells could have a functional role in the control of pre-B growth and differentiation by the hematopoietic microenvironment.

B-Lymphocytes↗