Type 1 diabetes mellitus is an autoimmune disease in which the body's immune cells attack
the insulin-producing cells of the pancreas. Several environmental and genetic factors may
predispose individuals to developing this disease, including changes in a gene called CD152.
This study will examine how this gene may influence the development of insulin-dependent
Patients with Type 1 diabetes mellitus enrolled in clinical trials at the National
Institutes of Health and at the University of Florida and healthy normal volunteers may
participate in this study. Participants will have up to three blood samples drawn over a
period of less than 1 year. The first sample (about 20 milliliters, or 4 teaspoons), will
be examined for changes in the structure of the CD152 gene. If the CD152 structure is
different from that normally seen in the general population, a second sample (about 90 ml,
or 6 tablespoons of blood) will be drawn. This sample will be used to study the function of
specialized immune system cells (T cells), including their growth and survival, chemicals
they produce when stimulated, and other factors. If these cells function differently from
what is generally seen in the population, a third sample (90 ml) will be drawn for more
This investigation may help explain what makes certain individuals susceptible to Type 1
diabetes mellitus and may contribute to the development of improved treatments for the
Genetic variations in CD152 have been reported to confer susceptibility to the development
of type-1-diabetes mellitus (T1DM). In this protocol we will draw blood samples from
patients and normal control volunteers in order to analyze for the presence of CD152 genetic
variations and to determine whether those variations are associated with measurable
abnormalities in T cell function. Subjects with T1DM and homozygous CD152 gene
polymorphisms, patients with T1DM but without CD152 polymorphisms, and control subjects with
or without CD152 polymorphisms will be studied to determine whether the CD152 polymorphisms
have measurable effects on T cell function and signaling. We will assess T cell function by
measuring: proliferation, viability, apoptosis, cytokine production and T cell signal
transduction. The identification and characterization of genes that are linked to T1DM may
provide an explanation into the mechanisms by which individuals are predisposed to T1DM.
Patients must have a willingness and legal ability to give consent, or permission.
Candidates with T1DM or Healthy Volunteers will be eligible.
Patients must be equal to or greater than 18 years of age.
Patients must not have an active malignancy.
Patients with a hemoglobin count of less than 9.0 mg/dl will be excluded. Patients may be
on erythropoietin therapy, but will not be placed on therapy solely to facilitate research
Patients must not have a known immunodeficiency syndrome.