Catherine Calkins, PhD
Philadelphia, PA 19107
Research and Clinical Interests
One project on-going in my laboratory is an investigation of the normal mechanisms of regulating immune responsiveness to self antigens.
Specifically, we are studying the response to self erythrocytes (MRBC) in normal BALB/c mice and in NZB mice that spontaneously develop anti-MRBC responses by 6-9 months of age. We have demonstrated that both T and B cells reactive to self erythrocytes are present in normal as well as autoimmune mice. In culture, development of anti-erythrocyte autoantibody responses depend upon CD4 positive helper T cells and can be suppressed by CD8 positive T cells. Studies in the literature have suggested that the NZB autoantibodies are specific for Band 3 on erythrocyte membranes. In collaboration with Dr. Peter Curtis (Department of Microbiology), we are investigating the specific epitope on the Band 3 molecule that is recognized by NZB autoantibodies and by the autoimmune B cells detectable in normal mice. We will also determine if there are any changes in the fine specificity of the anti-self erythrocyte response throughout the course of the autoimmune disease in the NZB mice.
The second project, being done in collaboration with Dr. Mark Feitelson (Dept. of Pathology), is an investigation of the immune responses that cause chronic hepatitis B. We are studying a mouse model of the disease in which immunodeficient SCID mice, expressing HBV as a transgene, are given immunocompetent lymphocytes as adults. After 3-12 weeks, these mice begin to show signs of hepatitis, including liver enzymes in the circulation, loss of HBV envelope expression in the liver, and cellular infiltrates into the liver. We are now analyzing the immune cells of these mice to determine the nature of the immune reactivity to HBV in terms of specificity and cytokine production, size of response and timing. We are also comparing the responses developed during chronic disease with those developed during acute disease in order to gain an understanding of the regulatory mechanisms contributing to development of disease.
Most Recent Peer-Reviewed Publications
- Laser microdissection coupled with RNA-seq reveal cell-type and disease-specific markers in the salivary gland of Sjögren's syndrome patients
- Regulatory T cells essential to prevent the loss of self-tolerance in murine models of erythrocytespecific autoantibody responses
- Rabies virus glycoprotein as a carrier for anthrax protective antigen
- Transient inhibition of Th1-type cytokine production by CD4+ T cells in hepatitis B core antigen immunized mice is mediated by regulatory T cells
- Different response requirements for IFNγ production in ELISPOT assays by CD4+ T cells from mice early and late after immunization
- T cells infiltrating the skin of Tsk2 scleroderma-like mice exhibit T cell receptor bias
- Evidence that the soluble factors secreted by activated immune cells suppress replication of human neurotropic JC virus DNA in glial cells
- Differences between normal and autoimmune T cell responses to autologous erythrocytes and haemoglobin: Impairment of haptoglobin-mediated inhibition in NZB spleen cells
- Expression and regulation of a recurrent anti-erythrocyte autoantibody idiotype in spleen cells from neonatal and adult BALB/c mice
- Cytokine secretion by C3H-lpr and -gld T cells: Hypersecretion of IFN-γ and tumor necrosis factor-α by stimulated CD4+ T cells
- Maintenance and Cure of the L5178Y Murine Tumor-dormant State by Interleukin 2: In Vivo and in Vitro Effects
- Evidence for regulation of the autoimmune anti-erythrocyte response by idiotype specific suppressor T cells in NZB mice
- Characterization of the spontaneous autoimmune (anti-erythrocyte) response in NZB mice using a pathogenic monoclonal autoantibody and its anti-idiotype
- Suppressor T cells and self-tolerance: Active suppression required for normal regulation of anti-erythrocyte autoantibody responses in spleen cells from nonautoimmune mice
- Development of self-tolerance in normal mice. Appearance of suppressor cells that maintain adult self-tolerance follows the neonatal autoantibody response
- Active role of T cells in promoting an in vitro autoantibody response to self erythrocytes in NZB mice
- Effect of antigen priming on T-cell suppression. I. Activity of Ly 1+2+ feedback suppressor T-cell precursors after isolation from competing Ly 2- T cells
- Rapid loss of feedback suppressor T-cell activity after priming in vivo
- Modulation in vivo of Lyt 2 antigen expression on T cells by anti-Lyt 2 antibody: Effects on Con A-induced unresponsiveness
- Detection of antibody-induced feedback suppression in spleen cell populations of primed and unprimed mice.