Cytotoxic and enhancing properties of early gammaM alloantibodies elicited by first set renal allografts. In vitro and in vivo studies with rat and guinea pig complement on somatic target cells with varying antigen density.

First set rat renal allografts transplanted over the strong Ag-B histocompatibility locus elicit antibodies of the gammaM class demonstrable at the time of graft rejection. These early gammaM alloantibodies with guinea pig complement are cytotoxic in vitro to high antigen density target cells like lymph node cells and splenocytes but not to low antigen density target cells like thymocytes and bone marrow cells. With rat complement, gammaM alloantibodies are required in far greater amounts to kill some high density target cells. This in vitro discrepancy between rat and guinea pig complement is not caused by the presence of natural antibody in guinea pig serum nor by a deficiency of complement components in rat serum, but is dependent on the antigen antibody interaction studied. In vivo studies show early gammaM alloantibodies to be cytotoxic to donor lymphoid cells but to enhance renal allografts. These cytotoxic and enhancing qualities reside in the same preparation of immunoglobulin and are influenced by antigen density. These studies suggest that the failure to damage donor kidneys by early, probably low avidity, antibody is caused by a low concentration of antigen on the endothelial cells within the renal graft, and or an inability of this antibody antigen interaction to activate syngeneic complement.

The role of antibody in rat renal allograft rejection. I. Absence of antibody to erythrocyte-associated antigens is associated with enhanced renal allograft survival.

Three biweekly infusions of a x 10(10) highly purified LEW (RT1l) erythrocytes (LEW-E) administered to BN (RT1n) rats commencing at 1 month of age failed to elicit alloantibody or cell-mediated cytotoxicity against LEW target cells. The magnitude of the proliferative response of lymphocytes taken from LEW-E-infused BN rats in unilateral mixed lymphocyte culture against LEW stimulator cells was identical to that of control BN lymphocytes. LEW renal grafts inserted in LEW-E-infused BN rats showed a markedly prolonged survival which was specific since Wistar (RT1u) renal allografts were acutely rejected. LEW kidneys grafted to unmodified and LEW-E-infused BN recipients elicited cytotoxic antibody responses to Ia-like antigens and cellular immune responses of identical magnitude and specificity. On the other hand, LEW renal grafts evoked hemagglutinating alloantibody in control BN recipients but failed to do so in LEW-E-infused BN recipients. This unresponsiveness to LEW-E-associated antigens was specific since Wistar renal grafts elicited anti-Wistar hemagglutinin responses in LEW-E-infused BN recipients. These results suggest that antibodies to LEW-E-associated alloantigens play an essential role in the acute rejection of LEW renal grafts by BN recipients.

Immunohistochemistry of Nasopharyngeal (Waldeyer's ring equivalent) lymphoid tissue in the rat.

Previously we have described the presence of Waldeyer's ring equivalent (WRE) lymphoid tissue in the rat, and pointed out the importance of such an experimental model for studying the immunological role of nasopharyngeal lymphoid tissue. Here we extend this work with immunohistological data in terms of compartmentalization and distribution of the various lymphoid and non-lymphoid cells of this WRE lymphoid tissue in situ. WRE tissue consists of distinct T cell and B cell areas. B cell areas predominate; they are located directly under the mucosal epithelium and consist mainly of follicles. These follicles frequently contain a germinal center with IgD negative B cells interspersed with scattered CD4 (helper/inducer) T cells. Follicular dendritic cells are present in the germinal centers. T cell areas, on the other hand, are predominantly present at the abluminal side of the WRE in interfollicular areas. In these areas high endothelial venules and both CD4 and CD8 (suppressor/cytotoxic) T cell populations with a clear preponderance of CD4 over CD8 cells can be observed. MHC class II positive interdigitating dendritic cells are also scattered throughout these T cell areas. Mononuclear phagocytes (ED1-positive monocytes/macrophages) are scattered throughout the WRE, but especially in the T cell areas. A subpopulation of (ED3-positive) mononuclear phagocytes, e.g., the lymphoid tissue macrophage, is exclusively scattered between the small blood vessels along the abluminal side of the lymphoid tissue. Here, plasma cells, including those of the IgA type, are located. The data show that nasopharyngeal lymphoid tissue in the rat can be considered as an immunologically fully equipped and active mucosal lymphoid organ presumably executing similar immune functions as the tonsils in the human Waldeyer's ring.

The Waldeyer ring equivalent in the rat. A model for analysis of oronasopharyngeal immune responses.

By means of serial sectioning of the head and neck a paired, rod shaped, parachoanic lymphoid organ was identified in Lewis rats. Histological, ultrastructural studies and FACS analysis showed this organ to be a lympho-epithelial organ with high endothelial venules (HEV) and a preponderance of B over T and T helper over T suppressor cells. Consequently this organ resembles the pharyngeal tonsil of man, and it is called the Waldeyer ring equivalent (WRE). The lymphatic drainage of this organ occurs predominantly to the deep, and to a lesser extent to the superficial cervical lymph nodes. Migration studies with 51Cr labeled cells show that the WRE lymphoid cells migrate into the lymphoid organs with HEV (peripheral lymph nodes. Peyer patches and WRE). In this respect they resemble peripheral lymph node cells more than cells from the Peyer patches. Thus the WRE lymphoid tissue in the rat is undoubtedly involved in local oronasopharyngeal immune surveillance and may also contribute to mucosal and systemic immune responses.

Tonsillar (Waldyer's ring equivalent) lymphoid tissue in the rat: lymphocyte subset binding to high endothelial venules (HEV) and in situ distribution.

We have studied lymphocyte traffic to the Waldeyer's ring equivalent (WRE) lymphoid tissue of the rat, by measuring the in vitro binding of various lymphocyte subsets to high endothelial venules (HEV) in the WRE. In addition, we studied the in situ distribution of these lymphocyte subsets. WRE tissue consists of B and T cell areas; the latter contain HEV. B cells outnumber T cells, and T helper (CD4) cells outnumber T suppressor/cytotoxic (CD8) cells (T/B ratio = 0.7; CD4/CD8 ratio = 5.1). In vitro studies of lymphocyte binding showed that lymphocytes adhere almost equally well to HEV in WRE tissue as to HEV in lymph node (LN) tissue, and much better to HEV in WRE than to HEV in Peyer's patch (PP) tissue. T cells bind better than B cells to HEV in WRE (T/B binding ratio = 1.8), and CD8 cells better than CD4 cells (CD8/CD4 ratio of 2.9-3.2, dependent on cell source). The observed preference of T over B cells in binding to HEV is not reflecting the distribution of these lymphocyte sets in situ. In this respect the WRE takes a unique position, since in other lymphoid organs T/B binding ratios parallels T and B cell distribution in situ. This may suggest a much more rapid passage of T cells through the WRE than through other lymphoid tissues, although other mechanisms cannot be ruled out. The CD8/CD4 binding ratio to HEV in WRE contrasts with situ distribution of these cells also; however, this is found for LN and PP lymphoid tissue too.(ABSTRACT TRUNCATED AT 250 WORDS)