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Studies on T Cell Clonal Expansion

II. The in Vitro Differentiation of Pre-Killer and Memory T Cells¹

From the Departments of Medicine and Microbiology of the Johns Hopkins University School of Medicine and the O'Neill Memorial Research Laboratories of the Good Samaritan Hospital, Baltimore, Maryland

Abstract

Spleen cells from C57BL/6 mice immunized with a DBA/2 mastocytoma (P815) were harvested at various stages of the immune response and cultured in vitro in the presence and absence of antigen.

Killer T cell activity in immune spleens could not be demonstrated until 6 or 7 days after antigen, but spleen cells harvested as early as 3 or 4 days and cultured for 24 hr at 37°C showed significant cytotoxicity. This increased activity was not augmented further by culturing with antigen.

"Memory" T cells, whose in vitro differentiation into killer cells required the presence of antigen, could not be demonstrated until 9 or 10 days after alloantigenic stimulation. Once produced, however, these cells persisted for at least 6 months. Memory cells, like killer T cells bound avidly to homologous allogeneic monolayers.

There were indications that the memory T cell pool was heterogeneous. On one hand, when cells harvested 10 days after stimulation were exposed to antigen in vitro, their lytic activity increased within 24 hr but showed no further increases when the culture period was extended. In contrast, 45-day-old immune cells showed increasing lytic activity throughout a 4-day exposure to antigen. Augmentation of lytic activity in both cell populations was independent of DNA synthesis through the first 24 hr of culture. Subsequent increases in the activity of 45-day cells was dependent upon cell proliferation.

Both the antigen-independent augmentation of lytic activity which followed culturing of immune cells, and the antigen-induced differentiation of memory cells were reversibly inhibited by a series of drugs which raised lymphocyte cAMP levels.

Footnotes

¹ This work was supported by Grant AI 10280 from the National Institute of Allergy and Infectious Disease and Contract NO1-CB-43965 from the National Cancer Institute. This is Communication No. 220 from the O'Neill Memorial Research Laboratories. Memorial Research Laboratories.

² Recipient of Research Career Development Award AI 70393 from the National Institute of Allergy and Infectious Disease.