Research Interests
T Lymphocytes are normally tolerant to the cells, tissues and molecules that characterize our self-constituents as a result of “education” processes associated with T cell development in the thymus. However, in autoimmune diseases such as systemic lupus erythematosus T cells appear that react to various self-molecules, indicating that T cell tolerance mechanisms have failed. A lupus-like disease can also be induced by chronic exposure to certain medications, and our studies suggest that these drugs act to prevent the acquisition of self-tolerance during T cell development in the thymus (figure).
We are studying the cellular and molecular basis for the capacity of lupus-inducing drugs to disrupt central T cell tolerance. This work employs mouse thymocytes undergoing development in in vitro model systems that mimic some of the process taking place in the thymus. CD4+CD8+ immature thymocytes transgenic for a T cell antigen receptor specific to a peptide from pigeon cytochrome c are induced to differentiate into mature CD4+ T cells in the presence of analogs of the cognate peptide. We are investigating the capacity of various drugs and environmental agents to enhance the responsiveness of cells undergoing selection in this system, a measure of autoreactivity. We are also interested in characterizing the gene products associated with compromised T cell function.
In related work we have developed a mouse model for drug-induced lupus in which autoreactive T cells and anti-chromatin autoantibodies develop after injection of a lupus-inducing drug into the thymus. This animal model will be useful in understanding the immunopathogenesis of this type of autoimmune disease as well as the origin of autoreactive B cells that have the same specificity as those is systemic lupus erythematosus.
Information about post-doctoral positions.
Selected Publications
Link to PubMed
Kretz-Rommel, A. and Rubin, R. L. (1999) Persistence of
autoreactive T cell drive is required to elicit anti-chromatin
antibodies in a murine model of drug-induced lupus. J. Immunol. 162,
813-820.
Kretz-Rommel, A. and Rubin, R. L. (2000) Disruption of positive
selection of thymocytes causes autoimmunity. Nature Medicine 6, 298-305.
Kretz-Rommel, A. and Rubin, R. L. (2001) Early cellular events in
systemic autoimmunity driven by chromatin-reactive T cells. Cellular
Immunology 208, 125-136.
Rubin, R. L., Salomon, D. R. and Guerrero, R. S. (2001) Thymus function
in drug-induced lupus. Lupus 10, 795-801.
Rubin, R.L. and Kretz-Rommel, A. (2001) A non-deletional mechanism for
central T cell tolerance. Critical Reviews in Immunology, 21, 29-40.
Rubin, R. L., Teodorescu, M., Beutner, E. H., and Plunkett, R.W. (2004)
Complement-fixing properties of antinuclear antibodies distinguish
drug-induced lupus from systemic lupus erythematosus, Lupus 13: 249-256.
Rubin, R. L. and Kretz-Rommel, A. (2004) Drug-Induced Autoimmunity. In
Stem Cell Therapy of Autoimmune Disease, R.K. Burt and A. Marmont, eds,
R.G. Landes Biosciences, Georgetown, TX, 173-181.
Rubin, R. L. Antihistone antibodies. (2004) In Systemic Lupus
Erythematosus, 4th edition, R.G. Lahita, ed., Elsevier Academic
Press, San Diego, 325-348.
Teodorescu, M., Ustiyan V., Russo, K. and Rubin, R. L. (2004) Binding
to histone of an anomalous IgG from patients with SLE and drug-induced
lupus, J. Clin. Immunol. 110:145-153.
Rubin, R. L. and. Hermanson, T. M. (2005) Plasticity in the
positive selection of T cells: affinity of the selecting antigen and
IL-7 affect T cell responsiveness, International Immunology 17: 959-971.
Rubin, R. L. (2005) Drug-induced lupus, Toxicology, 209: 135-147.
Rubin, R. L. (in press) Central and peripheral tolerance, In
Autoantibodies and Autoimmunity: Molecular Mechanisms in Health and
Disease, K. M. Pollard, ed., Wiley-VCH.
Rubin, R. L., Hermanson, T. M., Bedrick, E. J., McDonald, J. D.,
Burchiel, S.W., Reed, M. D. and Sibbitt, W. L. (2005) Effect of
cigarette smoke on autoimmunity in murine and human systemic lupus
erythematosus, Toxicological Sciences, 87: 86-96.
