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Phytohemagglutinin Unresponsiveness in Mouse Spleen Cells Induced by Methylcholanthrene Sarcomas¹

Tumor Biology Unit, Department of Pathology, University of Florida, College of Medicine, Gainesville, Florida 32601

The composition of spleen cell populations and the response of spleen cells in vitro to phytohemagglutinin (PHA) were studied in mice bearing methylcholanthrene-induced sarcomas and mice immunized with membrane antigen. With the use of discontinuous albumin density gradients to separate spleen cell suspensions, it was found that tumor-bearing mice and immunized mice had a shift in their spleen cell population, with a depletion of the dense, small lymphocyte population and a majority representation of a less dense, large mononuclear cell population.

The PHA reactivity of the spleen cells from the tumor-bearing and immunized mice was less than normal. This finding correlated with the shift in the spleen cell population because the less dense cell types respond minimally to PHA. In mice in which the tumors were excised, the PHA response of the whole spleen cell population returned to normal.

Our findings with the tumor-bearing mice suggest that a poor response to PHA may not be indicative of an immune deficiency but rather may demonstrate the possibility that the mice are undergoing an active immune response to their tumors. In human cancer patients, a poor peripheral lymphocyte response to PHA and an inability to demonstrate delayed hypersensitivity reactions have been interpreted as indication of an immune deficiency. However, it could be speculated that these findings in these patients may also suggest the presence of an active immune response to their tumors, rather than an immune deficiency. At present, this speculation provides a different working hypothesis for the evaluation of the immune status of cancer patients.

¹ Supported in part by American Cancer Society Grants ACS-T-463 and IN-62-G, Florida Division of the American Cancer Society Grant F-7-OUF, National Institute of Child Health and Human Development Grant HD-00384, National Institute of General Medical Sciences Grant GM-01996, and Training Grant AI-00401 in cellular immunobiology from the National Institute of Allergy and Infectious Diseases.

² Present address: Fort Detrick, Md. 21701.

³ To whom requests for reprints should be addressed, at Department of Pathology, College of Medicine, University of Florida, Gainesville, Fla. 32601.

Received 1/ 8/71. Accepted 2/23/71.