Biomedical subjects

Carolyn T A Herzig

Publications and source records attributed to Carolyn T A Herzig.

7 recordsLinked to original sources

PubMed2006

Comparison of gene expression by co-cultured WC1+ gammadelta and CD4+ alphabeta T cells exhibiting a recall response to bacterial antigen.

Immunization of cattle with a Leptospira borgpetersenii serovar hardjo-bovis vaccine results in the development of a recall response by WC1(+) gammadelta T cells and CD4(+) alphabeta T cells characterized by proliferation and interferon-gamma production. It was hypothesized that these two T cell subpopulations had largely redundant effector functions, principally differing in their requirements for activation. To test this, gene expression in cells proliferating to antigen were compared utilizing RT-PCR and bovine microarrays. Both T cell populations had similar transcript profiles for effector molecules, including IFN-gamma, FasL and granzyme B. In contrast, transcripts for costimulatory receptors and ligands were notably different following activation, as WC1(+) T cells expressed no or lower levels of transcripts for CD28 and CD40L, while CD4(+) T cells expressed substantial levels of both. However, both cell types had high levels of CTLA-4 transcript suggesting the cells may be regulated similarly following activation but differ in their need for and ability to provide costimulation. Microarray analyses to extend the number of genes examined revealed that while both subpopulations upregulated anti-apoptotic genes as well as those involved in cell activation and protein biosynthesis, overall there were limited differences between the two antigen-activated cell populations. Those genes that did differ were involved in cell signaling, protein production and intracellular protein trafficking. These results strengthen the hypothesis that these particular activated WC1(+) and CD4(+) T cells have overlapping effector functions and therefore may differ principally with regard to how they are recruited into immune responses.

Animals↗

PubMed2006

Identification of three new bovine T-cell receptor delta variable gene subgroups expressed by peripheral blood T cells.

To understand the biology of gammadelta T cells in ruminants, it is necessary to have a comprehensive picture of gammadelta T-cell receptor gene diversity and expression. In this study, three new subgroups of bovine T-cell receptor delta (TRD) variable genes were identified by RT-PCR and sequencing and homology with TRDV genes from other mammals determined. Previously unidentified TRDV subgroup genes described in this study include the bovine homologues of ovine TRDV2, TRDV3, and TRDV4 which were named accordingly. TRDV2 subgroup has two genes (TRDV2-1 and TRDV2-2) while we found the previously identified TRDV1 has at least eight genes corresponding to separate genomic sequences. Nucleotide and amino acid sequences for particular gene subgroups between cattle and sheep were more than 87% identical but identities among TRDV subgroups within a species were much less, with bovine TRDV4 having <45% identity to the other three bovine TRDV gene subgroups. Analysis of circulating bovine gammadelta T cells revealed that genes from all four TRDV subgroups were expressed in combination with TRDJ1, TRDJ3, and TRDC, although TRDV4 was the least represented, and all displayed a variety of CDR3 junctional lengths. Finally, some genes within the TRDV1, TRDV2, and TRDV3 subgroups recombined with TRAV incorporating TRAJs, suggesting dual use.

Amino Acid Sequence↗

PubMed2006

Characterization of WC1 co-receptors on functionally distinct subpopulations of ruminant gamma delta T cells.

WC1 molecules are implicated in augmenting cellular activation as well as inducing cell cycle arrest of gammadelta T cells. Since WC1 is a large multigene family differences in outcome could result from modulation of different WC1 molecules. To further investigate this family of molecules, peripheral blood WC1(+) gammadelta T cell subpopulations were evaluated by 2-D Western blotting and RT-PCR. We found 13 cDNA intracytoplasmic tail sequences with differences in signaling motifs among them and at least 20 biochemically distinguishable WC1 spots associated with cell membranes, with some in lipid rafts. An understanding of the diversity of 2-D spots could not be resolved by evaluating T cell clones, removing sialyated carbohydrates or blotting with anti-WC1.1 or anti-WC1.2-specific antibodies. Nevertheless, while the major gammadelta T cell subpopulations in blood (WC1.1(+)/WC1.2(-) and WC1.2(+)/WC1.1(-)) both had complex 2-D patterns, virtually all spots associated with WC1.2(+)/WC1.1(-) cells bore the WC1.2 epitope, distinguishing them from the WC1.1(+) cells.

Amino Acid Sequence↗

PubMed2006

Differential TCR gene usage between WC1- and WC1+ ruminant gammadelta T cell subpopulations including those responding to bacterial antigen.

Ruminant gammadelta T cells are divided into subpopulations based on the presence or absence of WC1 co-receptors (scavenger-receptor-cysteine-rich family members uniquely expressed on gammadelta T cells). Evidence suggests WC1+ are inflammatory while WC1- are regulatory and that they also differ in their tissue distribution. Recently, this paradigm was refined further as cells that produce interferon-gamma and proliferate to autologous antigens, leptospira antigens, or IL-12 were largely found within the WC1+ subpopulation that bears the WC1.1 antigenic epitope but not that bearing the WC1.2 epitope. Here, the T cell receptor gene expression by these different subpopulations (WC1-, WC1.1+, and WC1.2+) was compared using flow cytometrically-purified cells and reverse transcriptase-polymerase chain reaction (RT-PCR). The WC1- gammadelta T cells had transcripts for all 11 possible combinations of the TRG subgroup V and C genes while those in both WC1+ subpopulations were restricted to TRGV3-TRGC5 and TRGV7-TRGC5. In contrast, all three subpopulations expressed transcripts from all four known bovine TRDV genes. Further analysis of the WC1+ gammadelta T cells that proliferated in leptospira antigen-stimulated cultures indicated that they do not represent a unique subpopulation within the larger WC1+ population based on their TCR gene usage. Moreover, sequencing of 65 transcripts showed that their junctional regions were diverse as TRGJ5-1, TRGJ5-2, TRDJ1, and TRDJ3 were used, and CDR3s ranged from 9 to 24 amino acids. The restricted but shared gammadelta TCR gene usage for WC1.1+, WC1.2+, and WC1(+)-antigen-responsive cells leaves open the possibility that the WC1 co-receptor is an important determining element in the activation process and subsequent response.

Amino Acid Sequence↗

PubMed2006

Molecular cloning of bovine chemokine receptors and expression by WC1+ gammadelta T cells.

Chemokine receptors mediate leukocyte migration into secondary lymphoid tissues and localization to peripheral inflammation sites. We describe full-length cDNA sequences of bovine chemokine receptors CCR5, CCR7, CXCR3 and CXCR5 and transcript expression by WC1(+)gammadelta T cells, a unique cell population with proinflammatory characteristics that comprises a large proportion of mononuclear cells in young ruminants. Bovine chemokine sequences were more similar to those of humans than were murine sequences to humans', ranging from 84% to 91%. Transcript analysis showed that antigen stimulation of WC1(+)gammadelta T cells induced IFN-gamma production and substantially increased CCR5 and CXCR3 expression when compared with freshly isolated (ex vivo) cells. CCR7 transcripts were minimally expressed in ex vivo and proliferating WC1(+)gammadelta T cells and CXCR5 expression was negligible. These results confirm the proinflammatory nature of WC1(+)gammadelta T cells is reflected by its chemokine receptor expression and suggest WC1(+)gammadelta T cells are unlikely to transit through secondary lymphoid tissues.

Amino Acid Sequence↗

PubMed2005

Maternal thyroid hormone increases HES expression in the fetal rat brain: an effect mimicked by exposure to a mixture of polychlorinated biphenyls (PCBs).

Thyroid hormone is known to be essential for normal brain development both before and after birth, but much less is known about the role of thyroid hormone development before birth. In rodents, thyroid hormone of maternal origin can selectively regulate gene expression in the fetal cortex; HES1 was identified as a putative thyroid hormone responsive gene in the fetal cortex. Using in situ hybridization, we now confirm that thyroid hormone administration to pregnant rats can increase the abundance of HES1 mRNA in the fetal cortex on gestational day 16 (G16). In separate experiments, we found that maternal exposure to polychlorinated biphenyls (PCBs) increases HES expression similarly. Western analysis of proteins extracted from fetal cortex did not confirm that Notch-1 or Notch-3 activation was associated with treatment effects on HES expression. However, considering the role of HES proteins in fate specification of cortical neurons, these findings suggest that thyroid hormone, and PCB exposure, may influence fate specification of cortical neurons.

Analysis of Variance↗

PubMed2002

Thyroid hormone, brain development, and the environment.

Thyroid hormone is essential for normal brain development. Therefore, it is a genuine concern that thyroid function can be altered by a very large number of chemicals routinely found in the environment and in samples of human and wildlife tissues. These chemicals range from natural to manufactured compounds. They can produce thyroid dysfunction when they are absent from the diet, as in the case of iodine, or when they are present in the diet, as in the case of thionamides. Recent clinical evidence strongly suggests that brain development is much more sensitive to thyroid hormone excess or deficit than previously believed. In addition, recent experimental research provides new insight into the developmental processes affected by thyroid hormone. Based on the authors' research focusing on the ability of polychlorinated biphenyls to alter the expression of thyroid hormone-responsive genes in the developing brain, this review provides background information supporting a new way of approaching risk analysis of thyroid disruptors.

Brain↗