Pediatric Rheumatology Online Journal → August 2003 →  Basic Immunology  → Abstract #168

INCREASED g-IFN RESPONSES IN CD8+ T-CELLS FROM HCD6-TG MICE ARE NOT THE RESULT OF ALTERATIONS IN THE OVERALL TCR REPERTOIRE

N. G. Singer,¹ A. Abidi,¹ I. T. Soltys,¹ A. Valujskikh.²

¹Pediatrics, CWRU and Rainbow Babies and Children's Hosp., Cleveland, OH, United States; ²Immunology, Cleveland Clinic Foundation, Cleveland, OH, United States

CD6 is a T-cell co-stimulatory protein that is important during thymocyte development and in in vitro responses of mature T-cells to self-and allo-antigens. CD6 is increased on self-reactive T-cell clones in vitro and anti-CD6 mAbs inhibit this self-reactivity. Ex vivo depletion of CD6+ T-cells prior to bone marrow transplantation is useful to prevent graft-versus-host (gvh)disease. It is clinically useful to manipulate CD6 and its ligands therapeutically but the precise function(s) of CD6 is poorly understood. We hypothesize that CD6-dependent co-stimulation may be important during responses to MHC-antigen complexes with low functional avidity for their TCR (such as is so with self-antigen). To study CD6 function(s), we generated transgenic mice that both express human CD6 (hCD6) and overexpress total CD6. We examined peptide responses in our mice by immunizing them with OVA peptide to stimulate CD4+ T-cells or B-galactosidase peptide to stimulate CD8+ T-cells. Splenic T-cells were re-stimulated in vitro with syngeneic APC-peptide. ELIspots were performed for IL-2 and g-IFN. The data show that the frequency of antigen specific g-IFN secreting CD8+ T-cells is increased in hCD6-Tg mice compared with non-Tg controls. To determine if the T-cell repertoire prior to immunization is altered by expression of the hCD6 transgene we measured the frequency of VB TCRs in hCD6-Tg and non-Tg mice. The overall expression of VB TCR is similar in hCD6 Tg and non-Tg CD4 and CD8 T-cells. The TCR repertoire of CD8+ and CD4+ T-cells that lacked the hCD6 transgene was more restricted than that of cells that expressed the hCD6 transgene. For bone marrow transplants CD6-depletion may reduce gvh disease by altering the T-cell repertoire in such a manner as to reduce the amount and diversity of T-cells capable of responding to CD8-restricted host antigens. Future experiments will be directed at measuring effector function of hCD6 Tg CD8+ T-cells.