Cellular Immunity Against Rous Sarcomas of Chickens. Preferential Reactivity Against Autochthonous Target Cells as Determined by Lymphocyte Adherence and Cytotoxicity Tests In Vitro

Abstract

Spleen cells from random-bred chickens bearing Rous sarcomas were commonly more reactive against the neoplastic target cells'in autochthonous than in allogeneic interactions in vitro. This difference was observed both in cytotoxic assays (hCr release from labeled target cells) and in an immunoadherence test measuring attachment of $"Cr-labeled splenocytes to Rous sarcoma cells. Specific splenocyte reactivity was not observed with normal embryonic chicken fibroblasts, 3T3 cells, or embryonic mouse C3H fibro'blasts. The immunoadherence technique required only 2 hr to perform, and revealed a more consistent superiority of autochthonous recognition of Rous sarcoma cells than the cytotoxicity assay. Experiments in which both procedures were used simultaneously with identical cell populations yielded similar resiilts, indicating that splenocyte adherence may be a precursor of and/or concomitant to target cell damage and that individual-specific tumor antigencity may play a part in cellular immunity against Rouis sarcomas.The host-tumor relationship of chickens bearing Rous sarcomas has a number of advantages as a model pertinent to neoplasia in man. The tumor host is an outbred, nonlaboratory adapted animal, and the virus that induces the neoplastic transformation is one of a family of agents whose members are oncogenic in nature as well as in the laboratory, and active in a broad range of species in addition to the chicken (1). Cellular and humoral immunity in this system is well established both in vito and in vitro (2,3), and the chicken lends itself uniquely to the separation of lymphoid cell populations of diverse origin, and thereby to a differential definition of immunological capacity (4).The purpose of the present investigation was to compare splenocyte-target cell interaction in both autochthonous and allogeneic confrontations between Rous sarcoma cells and effector cells, by use of splenocytes sensitized during the course of the host's experience with a primary, actively growing tumor-a situation reflecting the only type of interaction that can be studied in man.This interaction was evaluated by a newly developed quantitative immunoadherence test, and by the cytotoxicity assay based on the liberation of labeled chromium from target cells.The [Medium 199 (Grand Island Biological Co., Grand Island, N.Y.) supplemented, with 5-10% inactivated calf serum (In Vitro, Jerusalem), 10% tryptose phosphate broth (Difco Laboratories), 200 units/ml of penicillin, 200 jg/ml of streptomycin, and 15-25 ml/liter of 5% NaHCOs]. The cells were washed by centrifugation, pooled, counted, and seeded.Other Cell Types. Normal chicken embryo cells (CEC) were secondary cultures (2-to 3-days-old) derived from 9-to 11-

Reactivity of serum from rous‐sarcoma‐bearing chickens with autochthonous and with allogeneic tumor cells: Preferential autochthonous recognition

“…with suspensions of either autochthonous or allogeneic sarcoma cells prior to use in a " crisscross " experiment (Wainberg et al, 1974) (Fig. 4).…”

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Complement-mediated cytotoxicity and indirect immunofluorescence assays showed that sera from random-bred chickens bearing Rous sarcoma ( R S)At least two distinct cell-surface antigens have been associated with chicken cells transformed by the Rous sarcoma virus (RSV): a virus sub-group-specific envelope antigen and an avian leukosis virus group-specific tumorassociated antigen (Gelderblom et al, 1972; Kurth and Bauer, 1972a, b).We have previously reported that splenocytes from randomly-bred Rous sarcoma-bearing chickens are specifically reactive against primary cultures of tumor cells (Wainberg et al, 1974). This was demonstrated by measuring both the immune adherence of 51Cr-labelled splenocytes to the neoplastic cells in vitro, and the capacity of the spleen cells to induce release of %r from labelled Rous sarcoma target cells.

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The expression and localization of surface neoantigens in transformed and untransformed cultured cells infected with avian tumor viruses

“…General applicability of this observation to other or all RSV tumor systems will be the subject of further investigation. The presence of such a unique antigen in RSV-induced chicken tumors has been indicated by the work of Wainberg et al (48). Moreover, Collins and Black (44) have described the occurrence of unique individual-specific antigens in SV 40-transformed hamster cells.…”

The thymus: Its influence on recognition of “self major histocompatibility antigens” by T cells and consequences for reconstitution of immunodeficiency

“…In addition, Mitchison [21], Thomas [22] and particularly Lawrence [-23] drew parallels between the transplantation reaction, i. e., the cellular immune response against tissue grafts expressing foreign MHC antigens and delayed type hypersensitivity against intracellular parasites or ocontact allergens. The similarity between these two cell-mediated immune reactions was formally demonstrated by the discovery that T cells involved in syngeneic immune functions express two types of specificities: One for self-antigens coded for by the MHC (//-2 in mice [-24-30], H L A in humans [, [31][32][33][34], AgB in rats [35], B in chickens [36,37]) and a second one for the foreign non-self antigen (X) (Reviewed in [38,39]). 1…”