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Generation of Cytotoxic T Lymphocytes in Vitro

VII. Suppressive Effect of Irradiated MLC Cells on CTL Response¹

From the Department of Immunology, Swiss Institute for Experimental Cancer Research, Lausanne, Switzerland and the Department of Pathology and the Franklin McLean Memorial Research Institute, University of Chicago, ³ Chicago, Illinois 60637

Abstract

Irradiated cells obtained from MLC at the peak of the CTL response caused profound suppression of generation of CTL when added in small numbers at the initiation of primary MLC prepared with normal spleen cells. The inhibitory activity of the MLC cells was not affected by irradiation (1000 rads) but was abolished by treatment with anti- serum and complement. The suppression was immunologically specific. The response of A (H-2^a) spleen cells toward C3H (H-2^k) alloantigens was suppressed by irradiated MLC cells obtained from MLC prepared with A spleen cells and irradiated C3H-stimulating cells, whereas the response of A spleen cells toward DBA/2 (H-2^d) alloantigens was affected relatively little. However, if irradiated C3H x DBA/2 F1 hybrid spleen cells were used to stimulate A spleen cells in MLC, addition of irradiated MLC cells having cytotoxic activity toward C3H antigens abolished the response to both C3H and DBA/2 antigens. The response to DBA/2 antigens was much less affected when a mixture of irradiated C3H and DBA/2 spleen cells was used as stimulating cells. Thus, the presence of MLC cells having cytotoxic activity toward one alloantigen abolished the response to another non-cross-reacting antigen only when both antigens were present on the same F1 hybridstimulating cells. This suppression of generation of CTL by irradiated MLC cells apparently involves inactivation of alloantigen-bearing stimulating cells as a result of residual cytotoxic activity of the irradiated MLC cells. This mechanism may be active during the decline in CTL activity noted in the normal immune response in vivo and in vitro.

Footnotes

¹ This work was supported by grants from the Swiss National Foundation for Scientific Research and United States Public Health Service Grants AI-4197 and AI-9268.

² Fellow, John Simon Guggenheim Memorial Foundation, 1974–1975.

³ Operated by the University of Chicago for the U.S. Energy Research and Development Administration under Contract E(11-1)-69.

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