Rat renal allograft tolerance is associated with local TGF-β and absence of IL-2r expression within chimeric immunocytic foci

• Published in: Transplantation proceedings Vol. 29; no. 4; pp. 2183 - 2184
• Main Authors: Hewitt, C.W., Strande, L., Santos, M., Goodman, M., Tarnoff, M., Zaontz, M.R., DelRossi, A.J., Doolin, E.J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.1997
• Subjects: Animals; Blood Transfusion; Graft Survival; Immunohistochemistry; Immunosuppression - methods; Kidney Transplantation - immunology; Kidney Transplantation - pathology; Rats; Rats, Inbred BN; Rats, Inbred Lew; Receptors, Interleukin-2 - biosynthesis; T-Lymphocytes - immunology; T-Lymphocytes - pathology; T-Lymphocytes, Regulatory - immunology; Transforming Growth Factor beta - analysis; Transplantation Chimera; Transplantation, Homologous
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/S0041-1345(97)00284-4

Tolerance was induced in Lewis (LEW) rat renal allograft recipients of Brown Norway kidneys by multiple pretransplant donor-blood transfusions and prior limited cyclosporine A. Rat renal allograft tolerance was associated with the induction of systemic donor T cells (10%), an early phase of nonspecific suppressor-cell generation, followed by maturation of systemic antigen-specific suppressor cells, and renal cellular infiltrates that develop long-term in situ in the kidney graft model. It was hypothesized that these infiltrates represent chimeric immunocytic foci that are locally regulated via a TGF-β-dependent mechanism. Both immunohistochemical staining and digital image analysis for cellular and extracellular TGF-β, IL-2 receptor (CD25), and the BN Class I-MHC marker (OX-27) were performed. Control rejecting (REJ) kidneys did not demonstrate any differences with respect to levels of infiltrating immunocyte area vs long-term surviving (TOL) kidneys (3.9% vs 4.5%, P = .303). Immunostaining with the BN Class I MHC marker (OX-27) demonstrated high levels of chimerism within immunocyte foci of the tolerant grafts (OX-27 BN+ immunocytes 49.0% ± 5.1%). In situ cellular IL-2 receptor (CD25) expression was demonstrated in REJ kidney infiltrates but not within TOL immunocytic infiltrating foci, when measured as percent of total lymphocytes (REJ = 5.0% vs TOL = 0.4%, P = .031). Conversely, TGF-β expression was significantly higher in immunocytes of TOL kidneys when measured as the number of DAB chromogen-staining pixels per total immunocyte area (TOL = .076 vs REJ = .047, P = .003). In conclusion, these results suggested that stable mixed immune chimerism (SMIC) plays an important role in DST-CyA-induced tolerance in situ. SMIC-induced tolerance may involve a local TGF-β-dependent mechanism that is associated with in situ TGF-β (+) and IL-2r (−) immunocytes.