The link between lymphocyte deficiency and autoimmunity: roles of endogenous T and B lymphocytes in tolerance.
We demonstrate that transfer of OVA-specific DO11 CD4(+) T cells into mice that lack T and B cells and produce secreted OVA as an endogenous self-protein results in a severe systemic autoimmune reaction with skin inflammation, wasting, and death. The transferred DO11 T cells undergo massive expansion and produce IL-2 and IFN-gamma abundantly. Transfer of DO11 cells into OVA-expressing animals in which T cells are absent but B cells are present, leads to mild disease with no death. In this situation, the DO11 cells undergo similar expansion but show poor Th1 differentiation. This regulatory effect of B cells correlates with profound TCR down-regulation. If T cells are present, the DO11 cells fail to expand independent of B cells. These results suggest that both endogenous T and B lymphocytes control T cell tolerance induction and pathogenicity, but at different stages of an anti-self response. Although endogenous T cells prevent expansion and maintain homeostasis, endogenous B cells limit subsequent effector responses of autoreactive CD4(+) T cells.
Department of Pathology, University of California, San Francisco, CA 94143, USA.
Birgit
B
Knoechel
Jens
J
Lohr
Estelle
E
Kahn
Abul K
AK
Abbas
D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D005260:Female; D007108:Immune Tolerance; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018448:Models, Immunological; D010047:Ovalbumin / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin