A Novel Lymphoproliferative / Autoimmune Syndrome Resembling Murine Iprigid Disease

In mice, the two distinct autosomal recessive genes lpr and gid can induce a syndrome characterized by autoantibody formation and the progressive accumulation of an unusual CD4-CD8T cell population in peripheral lymphoid tissue. This phenotype does not precisely mirror any human disease. In this report we describe two patients with a progressive lymphoproliferative disorder associated with autoimmunity. The peripheral blood and lymph nodes of these patients contained large numbers of an unusual CD4-CD8 T cell population. These CD4-CD8 T cells express surface markers characteristic of mature peripheral blood T cells (CD3, CD2, CD5), express the a/If form of the T cell receptor, and do not express surface markers characteristic of immature thymocytes (CD1) or NK cells (CD16, CD56). Functionally, these cells exhibited deficient proliferation and lymphokine production upon stimulation with mitogenic antibodies to CD3 or CD2. Both proliferation and lymphokine production could be augmented by co-stimulation with an antibody directed at the CD28 determinant. The clinical and immunological features of this syndrome resemble the lymphoproliferative/autoimmune disease seen in lpr and gid mice. (J. Clin. Invest. 1992.90:334-341.)