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Stephen I. Katz, M.D., Ph.D.

Portait Photo of Stephen Katz
Dermatology Branch
Senior Investigator
Center for Cancer Research
National Cancer Institute
Building 10, Room 12N238
Bethesda, MD 20892


Dr. Katz received his M.D. from Tulane University Medical School in 1966. He trained in dermatology at the University of Miami between 1967 and 1970. He then earned a Ph.D. in immunology from the University of London in 1974. He has been a member of many scientific advisory and editorial boards and currently also serves as director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases.


The long-term focus of my laboratory has been on the immune functions of skin with an emphasis on phenotypically and functionally characterizing its various constituents - particularly keratinocytes and Langerhans cells. Since the mid to late 1970's, a constant theme of my laboratory studies has been the role of Langerhans cells in the induction and elicitation of inflammatory skin diseases in mice. We 1) were the first to identify Langerhans cells as the only epidermal cells to synthesize and express class II MHC molecules in normal skin; 2) defined epidermal Langerhans cells to be bone marrow derived; 3) demonstrated the critical role of Langerhans cells in presenting haptens and proteins to T cells; 4) characterized the epitopes recognized by hapten-specific T cells; 5) showed that Langerhans cells become 'activated' after exposure to contact allergens; 6) identified some of the critical early events in the generation of contact sensitivity; and 7) elucidated the autocrine factors (IL-1beta) responsible for the migration of Langerhans cells from the epidermis; 8) demonstrated that keratinocytes (KC), through cytokine production, contribute to the perpetuation and amplification and, at times, to the suppression of inflammatory responses in skin; 9) found that keratinocytes can function as accessory cells for presentation of endogenous antigens expressed in the epidermis; and 10) demonstrated that self-peptides prolong survival in a mouse model of autoimmunity.

During the past 8 years the major emphasis of the laboratory has been on developing a better understanding of how and why the skin serves as a target for immune reactions as well as how the skin evades becoming a target for destruction. In addition, we have been focusing on how we can modulate the effector functions of CD8+ T cells so as to obviate tissue destruction. For these studies we developed transgenic mice that express a membrane-tethered form of a model self-antigen, chicken ovalbumin (mOVA), under the control of a keratin 14 (K14) promoter. K14-mOVA transgenic mice that express OVA mRNA and protein in the epithelia had been assessed for their immune responsiveness to OVA and are being used as targets for T cells obtained from OT-1 transgenic mice whose CD8+ T cells carry a Valpha2/Vbeta5-transgenic T cell receptor with specificity for the OVA257-264-peptides (OVAp) in association with class I MHC antigens. Some of the K14-mOVA transgenic mice develop a graft-vs-host-like disease (GVHD) when the OT-1 cells are injected while others appear to be tolerant to the OT-1 cells. We have recently identified IL-15 as a critical costimulator in determining whether immunity or tolerance ensues when OT-1 cells are adoptively transferred into these mice. We are continuing to pursue these studies to try to identify, at a molecular level, the critical factor(s) required for these OT-1 cells to become effector cells in the presence of IL-15.

We also developed transgenic mice that express soluble OVA under the control of a K14 promoter (K14-sOVA) that die within 5-8 days after adoptive transfer of OT-1 cells and identified these mice as a model for more acute GVHD-like reactions. Spontaneous autoimmunity occurred when these sOVA-mice were crossed with the OT-I mice. 83% of these sOVA/OT-I mice died during the first two weeks of life due to multiple-organ inflammation. In contrast, we found that preventive or therapeutic OVAp injections induced a dose-dependent increase in survival. Healthy survivors exhibited reductions in peripheral CD8 T cells, CD8-coreceptor- and V2-expression. Furthermore, CD8 T cells from healthy mice were anergic and could not be activated by exogenous IL-2. A block in IL-2/IL-7 signaling via the STAT5-pathway provided the basis for low surface expression of the CD8-coreceptor and failure of IL-2 to break CD8 T cell anergy. Thus, soluble T cell receptor ligand triggered multiple tolerance mechanisms in these sOVA/OT-I mice, making this treatment approach a potential paradigm for modulating human autoimmune diseases.

Finally, we are studying the mechanisms involved in the generation of a cytokine storm using our various peptides and our transgenic mouse models. The particular focus is on the cytokine profile that is induced during the cytokine storm.

This page was last updated on 12/12/2013.