The Journal of Immunology, Vol 144, Issue 1 47-52, Copyright © 1990 by American Association of Immunologists

ARTICLES

Induction of tolerance to parental marrow grafts in F1 hybrid mice. Evidence for recognition of self-antigens

M Nowicki, B Yankelevich, K Kikly and G Dennert
Immunology Program, University of Southern California, Kenneth Norris Jr. Comprehensive Cancer Center, Los Angeles 90033.

Lethally irradiated (C57BL/6xC3H)F1 mice are able to acutely reject parental C57BL/6 but not C3H marrow grafts, a phenomenon called hybrid resistance (HR). In attempts to inactivate this rejection mechanism we found that parental spleen cells activated with LPS are very potent in inducing tolerance to a subsequent C57BL/6 marrow graft. Tolerance is likely due to elimination of effector cells responsible for graft rejection as adoptive transfer of spleen cells from normal into tolerized mice reconstitutes responsiveness. Evidence is presented that the Ag on LPS-activated spleen cells responsible for induction of unresponsiveness are expressed on both C57BL/6 and (C57BL/6xC3H)F1 cells. This suggests that the HR effector cells recognize autoantigens. In support of this, induction of tolerance to C57BL/6 parental marrow grafts leads to a concomitant dramatic increase in endogenous CFU- spleen after a dose of gamma-irradiation. Moreover, elimination of the cells responsible for HR by injection of anti-ASGM1 antibody results in a similar increase of endogenous CFU-spleen after irradiation. It is concluded that HR is a reflection of autoimmunity, able to limit the proliferation of syngeneic marrow stem cells.

This article has been cited by other articles:

				M. H. Johansson, C. Bieberich, G. Jay, K. Karre, and P. Hoglund Natural Killer Cell Tolerance in Mice with Mosaic Expression of Major Histocompatibility Complex Class I Transgene J. Exp. Med., August 4, 1997; 186(3): 353 - 364. [Abstract] [Full Text] [PDF]