Avian scleroderma: evidence for qualitative and quantitative T cell defects.
T cell activation is dependent upon calcium influx and protein kinase C activation, with subsequent lymphocyte proliferation dependent upon IL-2. Abnormalities in T cell proliferation, including abnormal calcium influx and defective protein kinase C activation, have been identified in aged mice and humans and many autoimmune diseases including diabetes, lupus and scleroderma. Since UCD line 200 chickens, which spontaneously develop a scleroderma-like disease, have both thymic defects and a diminished peripheral blood lymphocyte response to IL-2, we have further investigated T cell function in these birds. Interestingly, line 200 T cells respond poorly in vitro to a variety of diversely acting T cell mitogens including concanavalin A, phytohemagglutinin and anti-chicken CD3 monoclonal antibody. Moreover, they do not respond well even to phorbol myristate acetate in conjunction with ionomycin. Addition of exogenous IL-2-containing supernatant concurrently with mitogenic stimulation also had no significant effect. Analysis of intracellular free calcium demonstrated that the lymphocytes from diseased birds had a reduced influx of calcium (or release for intracellular stores) following stimulation. These data clearly reflect a unique defect in T cell activation associated with avian scleroderma. Analysis of chicken CD3, CD4 and CD8 expression revealed a 39% decrease in peripheral blood CD4+ cells in scleroderma birds, although this decrease was not sufficient to explain the 80-90% decrease observed in proliferation assays and calcium influx. Our data support the hypothesis that avian scleroderma is mediated via abnormal function of lymphocyte co-stimulatory molecules or intracellular calcium regulators.
Wilson
T J
TJ
Department of Internal Medicine, University of California, Davis 95616.
Van de Water
J
J
Mohr
F C
FC
Boyd
R L
RL
Ansari
A
A
Wick
G
G
Gershwin
M E
ME
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D002118:Calcium / Q000378:metabolism; D002645:Chickens / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005805:Genes, MHC Class I; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000187:drug effects; D008934:Mitogens; D011201:Poultry Diseases / Q000235:genetics / Q000276:immunology*; D012595:Scleroderma, Systemic / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D016176:T-Lymphocyte Subsets / Q000187:drug effects
D000945:Antigens, Differentiation, T-Lymphocyte; D008934:Mitogens; D002118:Calcium