A novel lymphoproliferative/autoimmune syndrome resembling murine lpr/gld disease.
In mice, the two distinct autosomal recessive genes lpr and gld can induce a syndrome characterized by autoantibody formation and the progressive accumulation of an unusual CD4-CD8- T 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 alpha/beta 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 gld mice.
Sneller
M C
MC
Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Straus
S E
SE
Jaffe
E S
ES
Jaffe
J S
JS
Fleisher
T A
TA
Stetler-Stevenson
M
M
Strober
W
W
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D005434:Flow Cytometry; D006801:Humans; D006942:Hypergammaglobulinemia / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma