Surface membrane changes of T cells induced by syngeneic tumour cells. I. Formation and uptake of complexes of Ig and tumour antigens by T cells

Abstract

A large dose of tumour cells (10(7)) from two different tumours produced a significant increase of Ig-bearing spleen cells 6 h after intraperitoneal administration in syngeneic mice, like conventional antigens previously tested. Incubation of normal spleen cells in serum taken 6 h after administration of tumour cells reproduced in vitro the changes observed in the spleen cell population of the serum donors, demonstrating the presence of a cytophilic Ig, which was shown to be taken up by T cells. Serum collected 6 h after tumour cell inoculation contains also a 4S factor which can generate in vitro cytophilic Ig for T cells in the presence of a foreign soluble protein or tumour antigen. Extracts obtained from tumours cells, which were shown to contain tumour antigens, were labelled with 125I and mixed with the 4S factor and normal 7S Ig. Upon fractionation of the mixture, high molecular weight material containing radioactivity and 7S Ig were eluted in the void volume, well ahead of the position of both the tumour cell preparation and the 7S Ig. This material contained Ig cytophilic for splenic T cells and it is likely that it represents cytophilic complexes of Ig and tumour antigens. It is postulated that the cytophilic Ig detected in the serum of animals 6 h after injection of a large number of tumour cells represents cytophilic complexes of Ig and tumour antigens formed through the mediation of a soluble factor.

Surface membrane changes of T cells induced by syngeneic tumour cells. II. T‐cell defects induced by small tumour cell inocula or tumour cell antigens

“…Evidence has been reported which indicates that a membrane component from tumour cells promotes their growth in allogeneic mice and induces a form of immune tolerance especially if injected neonatally (Nowotny et al, 1974). The evidence presented in the previous communication in this series indicates that syngeneic tumours are able to induce what we have called a 6-h T-cell response (Dular et al, 1978). This phenomenon has been observed following injection of foreign proteins in Freund's complete adjuvant (FCA) or particulate antigens such as heterologous erythrocytes or bacteria (Paraskevas et al, 1972).…”

“…Soluble tumour cell antigens were prepared by papain digestion as described in the previous paper (Dular et al, 1978). Horse red blood cells (HRBC) were purchased from the National Biological Laboratory, Winnipeg.…”

“…The 6-h T-cell response was assayed by the determination of Ig+ cells in the spleens of animals as described in the previous communication (Dular et al, 1978). An increase in Ig+ cells is usually indicative of a positive 6-h T-cell response, especially when combined with the detection of the cytophilic Ig in the serum.…”

Detection in vivo 6 hours after immunization of a mediator with possible antisuppressor activity

“…A net increase of Ig' cells when spleen, or nylon wool-nonadherent cells (NWNC) are incubated with 6HS in vitro is detected by a very sensitive assay which utilizes a hybrid antibody [4] and is indicative of the presence of the cytophilic complexes. sumably complexes) has also been demonstrated in the serum after injection of tumor cells in syngeneic systems [6] or allogeneic cells (unpublished data). The complexes act as potent amplifier and antigen-specific factors which enhance the 7 S response [S, 71.…”

Factors inducing a loss of net negative surface charge on spleen cells of mice grafted with a slow-growing tumour

“…The existence of factors secreted by T cells has been revealed in tumour bearers (Treves et al, 1976;Subramanian et al, 1978) or in mice after antigenic stimulation (Suemura et al, 1977). Antigen-antibody complexes have been detected on T-cell surfaces which may regulate the immune response (Kontainen & Mitchison, 1975;Dular et al, 1978).…”