The Journal of Immunology, Vol 143, Issue 1 89-94, Copyright © 1989 by American Association of Immunologists

ARTICLES

T cell tolerance to self antigens in New Zealand hybrid mice with lupus- like disease

BL Kotzin, JW Kappler, PC Marrack and LR Herron
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.

We determined if self-reactive T cells are able to escape thymic tolerance in autoimmune New Zealand mice. T cells utilizing V beta 17a and V beta 11 encoded receptors have been shown to be clonally eliminated in nonautoimmune mice expressing I-E because of their potential self-reactivity. Similarly, V beta 8.1+ and V beta 6+ T cells are tolerized in the thymus of nonautoimmune mice that express Mls-1a. These T cell subsets were quantitated in the lymph nodes and spleens of (NZB x NZW)F1 and (NZB x SWR)F1 mice. In young mice from both autoimmune strains, deletion was similar to that observed in control animals matched for I-Ed and Mls-1a expression. Furthermore, older female autoimmune mice with elevated levels of IgG antinuclear antibodies and severe lupus-like renal disease did not demonstrate evidence of a global tolerance defect. We also found that the levels of residual V beta 17a+ cells in MHC-matched control F1 strains were further reduced by up to 80% in autoimmune (NZB x SWR)F1 mice. The greater in vivo elimination corresponded to an enhanced ability of NZB spleen cells, compared with other H-2d spleen cells, to stimulate V beta 17a+ hybridomas in vitro. The increased stimulation in culture could not be attributed to quantitative differences in I-E Ag expression. The results suggest that autoreactive T cells have been eliminated in these autoimmune mice by normal mechanisms of self- tolerance. Furthermore, the data demonstrate the existence of an NZB minor locus not present in other H-2d strains that influences T cell repertoire and enhances stimulation of T cells potentially reactive to self class II MHC Ag.

This article has been cited by other articles:

				V. Roy, N.-H. Chang, Y. Cai, G. Bonventi, and J. Wither Aberrant IgM Signaling Promotes Survival of Transitional T1 B Cells and Prevents Tolerance Induction in Lupus-Prone New Zealand Black Mice J. Immunol., December 1, 2005; 175(11): 7363 - 7371. [Abstract] [Full Text] [PDF]

				N.-H. Chang, R. MacLeod, and J. E. Wither Autoreactive B Cells in Lupus-Prone New Zealand Black Mice Exhibit Aberrant Survival and Proliferation in the Presence of Self-Antigen In Vivo J. Immunol., February 1, 2004; 172(3): 1553 - 1560. [Abstract] [Full Text] [PDF]

				J. Wither and B. Vukusic Autoimmunity Develops in Lupus-Prone NZB Mice Despite Normal T Cell Tolerance J. Immunol., November 1, 1998; 161(9): 4555 - 4562. [Abstract] [Full Text] [PDF]