phocyte and cytokine-directed stratergies for inhibiting skin allograft rejection in mice. Transplant Proc 1995; 27(1): 380. 40. Anderson GP, Coyle AJ. TH2 and “TH2-like” cells in allergy and asthma: pharmacological perspectives [see comments]. Trends Pharmacol Sci 1994; 15(9): 324. 41. Sayegh MH, Akalin E, Hancock WW, et al. CD28–B7 blockade after alloantigenic challenge in vivo inhibits Th1 cytokines but spares Th2. J Exp Med 1995; 181(5): 1869. 42. Chen ZK, Cobbold SP, Waldmann H, Metcalfe S. Amplification of natural regulatory immune mechanisms for transplantation tolerance. Transplantation 1996; 62(9): 1200. 43. Lowry RP, Takeuchi T, Cremisi H, Konieczny B. Th2-like effec- tors may function as antigen-specific suppressor cells in states of transplantation tolerance. Transplant Proc 1993; 25 (1 Pt 1): 324. 44. Nickerson P, Steurer W, Steiger J, Zheng X, Steele AW, Strom TB. Cytokines and the Th1/Th2 paradigm in transplantation. Curr Opin Immunol 1996; 6(5): 757. 45. Field EH, Gao Q, Chen N, Rouse TM. Balancing the immune system for tolerance. Transplantation 1997; 64(1): 1. 46. Abramowicz D, Vandervorst P, Bruyns C, Doutrelepont JM, Vandenabeele P, Goldman M. Persistence of anti-donor allo- helper T cells after neonatal induction of allotolerance in mice. Eur J Immunol 1990; 20: 1647. 47. Donckier V, Wissing M, Abramowicz D, et al. Early neutraliza- tion of IL-4 but not of IL-10 abrogates neonatal induction of transplantation tolerance in mice. Transplant Proc 1995; 27(1): 186. 48. Gao Q, Chen N, Rouse TM, Field EH. The role of IL-4 in the induction phase of allogeneic neonatal tolerance. Transplanta- tion 1996; 59: 1571. 49. Wasowska B, Wieder KJ, Hancock WW, et al. Cytokine and alloantibody networks in long term cardiac allografts in rat recipients treated with rapamycin. J Immunol 1996; 156(1): 395. 50. Hall BM. Mechanisms maintaining enhancement of allografts. I. Demonstration of a specific suppressor cell. J Exp Med 1985; 161(1): 123. Received 23 July 1997. Accepted 13 January 1998. 0041-1337/98/6509-1152$03.00/0 TRANSPLANTATION Vol. 65, 1152–1158, No. 9, May 15, 1998 Copyright © 1998 by Williams & Wilkins Printed in U.S.A. THE CELLULAR BASIS OF CARDIAC ALLOGRAFT REJECTION VIII. MECHANISMS UNDERLYING DELAYED ALLOGRAFT REJECTION IN PVG C6-DEFICIENT RATS 1 STEVEN MERTEN,JU CHUAN CHEN,HONG HA,KARREN PLAIN,ROCHELLE A. BOYD,MARK J. PENNY, PETER LEENAERTS, AND BRUCE M. HALL 2 Department of Medicine, University of New South Wales, Liverpool Hospital, Liverpool 2170, New South Wales, Australia Background. The delayed allograft rejection in C6- deficient PVG C6 2 rats compared with normal PVG rats has been attributed to the lack of alloantibody activation of the membrane attack complex of comple- ment. As T cells alone have been shown to effect graft rejection, we examined T-cell responses in PVG C6 2 rats. Methods. The cellular infiltrate and its mRNA for cytokines and effector molecules in DA heart allo- grafts to PVG and PVG C6 2 rats was compared by immunoperoxidase staining and semiquantitative re- verse transcriptase polymerase chain reaction. The ability of pure populations of T cells or alloantibody to mediate DA heart graft rejection in irradiated (750 rads) PVG and PVG C6 2 rats was also compared. Results. The median rejection time of DA heart allo- grafts was 8 days in PVG rats and 17.5 days in PVG C6 2 . PVG C6 2 rats sensitized to DA by two skin grafts rejected DA heart grafts in 5– 6 days. CD3 1 , CD4 1 , CD8 1 , interleukin-2 receptor-positive T cell, macro- phage, and natural killer cell infiltration, as well as class II major histocompatibility complex and inter- cellular adhesion molecule-1 up-regulation, in grafts was similar in naive PVG and PVG C6 2 rats. mRNA for T helper 1 cytokine interleukin-2, interferon-g, tumor necrosis factor-b, macrophage molecules tumor necro- sis factor-a, and inducible nitric oxide synthase, as well as cytotoxic T-cell effector molecules perforin and granzyme A and B, were found to be the same in the grafts from both naive PVG and naive PVG C6 2 rats. Thus, there appeared to be no difference in the T-cell effector response between the PVG and PVG C6 2 groups. There were higher alloantibody titers in PVG C6 2 rats than in PVG hosts. Irradiation ablated rejec- tion and alloantibody responses and reconstitution with naive T cells alone restored rejection in both PVG and PVG C6 2 rats. Irradiated rats given serum from PVG rats that had rejected DA grafts did not effect rejection of DA grafts even if given naive T cells. Sen- sitized T cells restored second set. Conclusions. PVG C6 2 rats have normal T-cell re- sponses and can mediate allograft rejection in the ab- sence of alloantibody. The failure of PVG C6 2 to reject 1 This work was supported by the National Health and Medical Research Foundation of Australia and a South Western Sydney Clinical School scholarship from the University of New South Wales (S.M.). 2 Address correspondence to: Bruce M. Hall, Department of Med- icine, Liverpool Hospital, P.O. Box 103, Liverpool 2170, New South Wales, Australia. TRANSPLANTATION 1152 Vol. 65, No. 9