The role of alpha beta+ T cells and homeostatic T cell proliferation in Y-chromosome-associated murine lupus.
Male BXSB mice develop an early life, severe lupus-like disease largely attributed to an undefined Y-chromosome-associated autoimmunity accelerator, termed YAA: Although the exact disease pathogenesis is uncertain, indirect evidence suggests that T cells play an important role in the male BXSB disease. We have developed TCR alpha-chain gene-deleted BXSB mice to directly examine the role of alphabeta+ T cells and the mode by which Yaa promotes disease in this strain. All disease parameters, including hypergammaglobulinemia, autoantibody production, glomerulonephritis, and the unique monocytosis of BXSB males, were severely reduced or absent in the alphabeta+ T cell-deficient mice. Adoptively transferred CD4+ T cells of either male or female BXSB origin showed equal homeostatic proliferation in alphabeta+ T cell-deficient male recipients. Moreover, deficient male mice eventually developed equally severe lupus-like disease after adoptive transfer and homeostatic expansion of T cells from wild-type BXSB males or females. The results directly demonstrate that the Yaa-mediated disease requires alphabeta+ T cells that are not, in themselves, abnormal in either composition or properties, but are engaged by a Yaa-encoded abnormality in a non-T cell component. In addition, homeostatic anti-self proliferation of mature T cells derived from a small number of precursors can induce systemic autoimmunity in an appropriate background.
Lawson
B R
BR
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Koundouris
S I
SI
Barnhouse
M
M
Dummer
W
W
Baccala
R
R
Kono
D H
DH
Theofilopoulos
A N
AN
D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005260:Female; D006706:Homeostasis / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007668:Kidney / Q000276:immunology / Q000473:pathology; D007964:Leukocytosis / Q000235:genetics / Q000276:immunology; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D014998:Y Chromosome / Q000235:genetics
D007074:Immunoglobulin G; D016693:Receptors, Antigen, T-Cell, alpha-beta