QUANTITATION OF THE CHANGES IN SPLENIC ARCHITECTURE DURING THE REJECTION OF CARDIAC ALLOGRAFTS OR XENOGRAFTS

Background. The spleen plays a central role in the generation of both cellular and antibody responses during graft rejection, Although chang es in lymphocyte function have been extensively analyzed in vitro, the re have been limited attempts at quantitating the structural changes i n the lymphoid compartments within the spleen during graft rejection. Methods. We describe here a means of quantitating the histological cha nges in the spleen using immunohistochemical techniques and computeriz ed image analysis. Results. Allograft rejection at 6 days after transp lant is characterized by a threefold increase in the T cell-rich areas of the periarteriolar lymphoid sheaths (PALs). The follicular areas a re enlarged and germinal centers appear in 55% of the white pulp regio ns. Acute xenograft rejection, 4 days after transplant, is specificall y accompanied by a 2.3-fold increase in the marginal zone (MZ) and an increase in the numbers of B cells in the red pulp of the spleen. The expansion of both PALs and follicular/germinal centers during xenograf t rejection is comparable to that observed during allograft rejection. We also investigated the effect of two immunosuppressants, leflunomid e and cyclesporine, on the spleen of rats with hamster hearts. Lefluno mide, which prevents acute xenograft rejection, prevented the increase in PALs and significantly reduced the areas comprising the MZ and fol licles. Cyclosporine, which does not alter the tempo of xenograft reje ction and only partially inhibited xenospecific antibody production, i nhibited the increase in PALs and the appearance of germinal centers, while permitting a modest increase in the area of MZ and follicles. Co nclusions. These observations collectively suggest that both T cell-de pendent and T cell-independent responses are stimulated by the transpl anted xenograft. However, the T cell-independent responses that initia te xenograft rejection are characterized by very modest increases in t he area of MZ and follicles within the white pulp of the spleen.