Abstract
Acute rejection is associated with the activation of helper and cytotoxic cells. A shifting balance between the suppressor/inducer CD45+ CD4+ and T helper/inducer (CD4+CD45−) cells may be responsible for the transition from quiescence to overt rejection. We examined the kinetics of CD45 expression on CD4+ T cells in renal allograft recipients from pretransplant values to acute rejection and after reversal of rejection, searching for a shift in balance between helper/inducer and suppressor/inducer cell subsets. Using two color flow cytometry, the peripheral blood levels of CD4+, CD4+CD45− [T helper/inducer (Thi)], CD4+CD45+ [T suppressor/inducer (Tsi)], CD3+, and CD8+ T cells subsets and their interrelationships, were determined in 49 patients prior to transplantation, and in 10 of them, during acute rejection and after its reversal. Results were analyzed and compared to data obtained from 10 healthy blood donors. Acute rejection was associated with a significant decline in CD45+ CD4+ expression compared to quiescent phase (22% ± 3.7%vs. 26.5% ± 3.2%, p = 0.05) and controls (29.5% ± 6.2%, p = 0.01). No difference was observed compared to pretransplant levels (19.9% ± 3.2%, p = ns). CD45−/CD45+ (Thi/Tsi) ratio was lowest during quiescence (0.75) compared to rejection (0.97, p = 0.05), in controls (0.98, p = 0.05) and pretransplant values (1.4, p = 0.01). Acute rejection was characterized by higher Thi/CD8+ and lower Tsi/CD8+ ratio (103 and 88 respectively, p = 0.045), compared to clinical quiescence (104 and 116 respectively, p = 0.039). These data suggest that acute rejection is associated with down regulation of CD4+CD45+ suppressor/inducer subset. This shift may account for the transition from quiescence to overt rejection, concurring with reports on CD4+CD45 regulatory function.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Waaga AM, Chandraker A, Apadafora-Ferriera M et al. Mechanisms of indirect allorecognition: characterization of MHC class II allopeptide-specific T helper cell clones from animals undergoing acute allograft rejection. Transplantation 1998; 65(7): 876–883.
Merville P, Lambert C, Durand I et al. High frequency of IL-10 secreting CD4+ graft infiltrating T lymphocytes in promptly rejected kidney allografts. Transplantation 1995; 59(8): 1113–1119.
Guo WH, Tian L, Chan KL et al. Role of CD4+ and CD8+ cells in early and late acute rejection of small bowel allograft. J Pediatr Surg 2001; 36(2): 352–356.
Beik AI, Morris AG, Higgins RM, Lam FT. Serial flow cyto-metric analysis of T-cell surface markers can be useful in the differential diagnosis of renal allograft dysfunction. Clin Transplant 1998; 12(1): 24–29.
De Ruysscher D, Waer M, Vandeputte M et al. Changes in lymphocyte subsets after local irradiation for early stage breast cancer and seminoma testis: long term increase of activated (HLA-DR+) T cells and decrease of 'naïve' (CD4-CD45R) T lymphocytes. Eur J Cancer 1992; 28A(10): 1729–1734.
Tilmant L, Dessaint JP, Tscicopoulus A et al. Concomitant augmentation of CD4+CD45+ suppressor/inducer subset and diminution of CD4+CDw29+ helper/inducer subset during rush hyposensitization in hymenoptera venom allergy. Clin Exp Immunol 1989; 76(1): 13–18.
Copin MC, Noel C, Hazzan M et al. Diagnostic and predictive value of an immunohistochemical profile in asymptomatic acute rejection of renal allografts. Transpl Immunol 1995; 3(3): 229–239.
Oliviera JG, Ramos JP, Xavier P et al. Microemulsion cyclosporin formulation in contrast to the old formulation, widens the T lymphocyte subsets differences between stable and acute rejection of kidney transplants. Nephrol Dial Transplant 2001; 16(6): 1256–1261.
Lehman M, Graser E, Risch K et al. Anti-CD4 monoclonal antibody-induced allograft tolerance in rats despite persistence of donor reactive T cells. Transplantation 1997; 64(8): 1181–1187.
Dollinger MM, Howie SE, Plevris JN et al. Intrahepatic proliferation of 'naïve and memory T cells during liver allo-graft rejection: primary immune response within the allograft. FASEB J 1998; 12(11): 939–947.
Hellund G, Dohlesten M, Ericsson PO, Sjorgen HO. Rapid response to Con A by CD4+CD45R- rat memory lymphocytes as compared to CD4+CD45R+ lymphocytes. Cell Immunol 1989; 119(2): 317–326.
Pawelec G. CD4+CD45R- suppressor-inducer T-cell clones: requirements for cellular interaction, proliferation and lymphokines for the induction of suppression in peripheral blood mononuclear cells. Immunology 1990; 69(4): 536–541.
Razziudin S, Elawad MF. Immuneregulatory CD4+CD45r+ suppressor/inducer T lymphocytes subsets and impaired cell-mediated immunity in patients with Down's syndrome. Clin Exp Immunol 1990; 79(1): 67–71.
Baxevanis CN, Papadopoulus NG, Katsarou-Katsari A, Papamichail M. Regulation of allergen specific immune responses by CD4+CD34r+ cells in patients with allergic contact dermatitis. J Allergy Clin Immunol 1994; 94(5): 917–927.
Muller C, Wolf H, Gottlicher J, Eibl MM. Helper/inducer and suppressor-inducer lymphocyte subsets in alcoholic cirrhosis. Scand J Gastroenterol 1991; 26(3): 295–301.
Weimer R, Zipperle S, Daniel V et al. Pretransplant helper function and interleukin-10 response predict risk of acute kidney graft rejection. Transplantation 1996; 62(11): 1606–1614.
Takehisa Y, Sakiyama S, Uyama T et al. Progressive increase of CD4(+)cd45rd(-) lymphocytes after allograft rat transplantation: a marker of acute rejection. J Thorac Cardiovasc Surg 2002; 124(4): 675–683.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Shabtai, M., Waltzer, W., Ayalon, A. et al. Down regulation of CD45 expression on CD4 T cells during acute renal allograft rejection: Evidence of a decline in T suppressor/inducer activity. Int Urol Nephrol 34, 555–558 (2002). https://doi.org/10.1023/A:1025641404743
Issue Date:
DOI: https://doi.org/10.1023/A:1025641404743