Flexibility of the thyroiditogenic T cell repertoire for murine autoimmune thyroiditis in CD8-deficient (beta2m -/-) and T cell receptor Vbeta(c) congenic mice.
In murine experimental autoimmune thyroiditis (EAT), previous studies have revealed a highly adaptable thyroiditogenic T cell repertoire which involves both CD4+ and CD8+ T cells in the susceptible H2k strain. To further test this flexibility, congenic B10.K mice lacking CD8+ T cells (B2m -/-) or harboring 70% T cell receptor (TCR) Vbeta gene deletions (Vbeta(c)) were immunized with mouse thyroglobulin (MTg) and evaluated for EAT 28 days later. All B2m -/- mice developed moderate antibodies to MTg, and thyroidal inflammation was comparable to B10.K mice, averaging 35-40%. Spleen cells (SC) from MTg-immunized mice were then injected into syngeneic recipients after stimulation in vitro with MTg or with conserved, thyroxine (T4)- or thyronine (T0)- containing 12mer peptides, hT4(5), hT0(2553), or hT4(2553), derived from the primary hormonogenic sites at position 5 or 2553 of human Tg. As previously shown in another H2k strain (CBA/J), all three peptides activated MTg-primed SC to transfer EAT in B10.K mice. hT4(5) and hT4(2553) were further tested in B10.K-Vbeta(c) and beta2m- B10.K mice. Both peptides expanded thyroiditogenic T cells in either strain, resulting in severe thyroiditis in syngeneic recipients. That EAT can develop in the absence of CD8+ T cells or in the presence of a severely restricted TCR repertoire underscores the remarkable flexibility of the thyroiditogenic T cell profile in the susceptible k haplotype.
Lomo
L C
LC
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan, USA.
Zhang
F
F
McCormick
D J
DJ
Giraldo
A A
AA
David
C S
CS
Kong
Y C
YC
D019264:Adoptive Transfer; D000818:Animals; D016827:CD8 Antigens / Q000378:metabolism*; D005260:Female; D006183:H-2 Antigens; D006239:Haplotypes; D006801:Humans; D007114:Immunization; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013954:Thyroglobulin / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000209:etiology / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics
D016827:CD8 Antigens; D006183:H-2 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D001613:beta 2-Microglobulin; D013954:Thyroglobulin