Professor Emeritus of Ophtalmology
|Address:||620 19th Street S
Birmingham, AL 35233
B.S. (Microbiology), Miami University, Ohio
M.S. (Microbiology) Indiana University
Ph.D. (Immunology), Harvard University
My research focuses on identifying mechanisms of inducing and abrogating immunological tolerance. Our long-term goal is to translate our findings into novel therapies for preventing graft rejection. We have previously determined that tolerance by oral or ocular administration of proteins induces CD8+ suppressor T (Ts) cells that can transfer unresponsiveness to naïve, syngeneic mice. Recently, we have developed the methodology to induce antigen-specific by stimulating CD8+ T suppressive cells from TCR transgenic (Tg) mice in the presence of TGFbeta. These T cells express FoxP3 inhibit the in vitro activation of CTL responses by normal B6 CD8+ T cells specific for s defined alloantigen but only if the alloantigen and the antigen recognized by the CD8+ T cells are presented by the same antigen presenting cells. The TGFbeta-activated TCR T Tg cells also suppressed the rejection of heterotopic vascularized cardiac allografts in normal mice mediated by specific CD4+ TCR Tg T cells, if the cardiac allograft expressed both antigens as transgenes. Prolonged survival of allografts was associated with rapid migration of the FoxP3+ CD8+ Ts cells into the donor hearts. We are also studying the transplantation of retinal pigment epithelial (RPE) cells as a treatment for age-related macular degeneration (AMD), which is the leading cause of blindness in people over the age of 65 in this country. This disease ultimately results from the loss of light sensing (photoreceptor) cells; however, the loss of photoreceptor cells is preceded by loss of the underlying RPE. Replacement of dead or damaged cells with healthy retinal cells is a very promising approach to the treatment of this, and other, retinal diseases that we are investigating. Although the eye is an immunologically privileged site, our preliminary data show that allogeneic RPE transplanted into the subretinal space of allogeneic mice are rejected within 4 weeks, whereas they are not rejected in syngeneic mice or immunodeficient Rag-1 knockout allogeneic mice. Our goal is to develop methods to prevent rejection by inducing tolerance. To this end, we have produced transgenic mice expressing OVA in the retinal cells, which will be transplanted into syngeneic mice that have been adoptively transferred with OVA-specific TCR transgenic T cells to track specific cellular interactions in vivo. Experiments are currently underway to determine whether RPE expressing OVA are rejected by OVA-specific T cells and whether rejection can be abrogated by induction of tolerance to OVA or by transfer of CD8+ TCR Tg T cells activated in the presence of TGFbeta.