Changes in the host lymphocyte subsets during chemical carcinogenesis.

Changes in small lymphocyte subsets in the lymphoid organs of young C3H mice were studied following i.m. injection of a carcinogenic dose of 3-methylcholanthrene in trioctanoin oil. Using monoclonal anti-Lyt antibodies and a sandwich radiolabeling method with 125I-labeled rabbit anti-mouse Immunoglobulin, the lymphocyte subpopulations in the thymus, spleen, and draining lymph node were examined by radioautography. During the fifth week following the administration of the carcinogen and prior to the appearance of histologically evident tumor cells, a sharp decrease in the level of Ly-1,2+ small lymphocyte population in the thymus was noted which coincided with a considerable increase (10-fold) in the Ly-2+ and a small increase (1.7-fold) in the Ly-1+ population. During the same period, a similar increase in the Ly-2+ population was also observed in the draining but not in the contralateral lymph node. The high levels of Ly-2+ cells lasted for more than 4 weeks in the thymus while, in the draining node, they lasted for 2 weeks and dropped to normal levels (0 to 2%) simultaneously with the appearance of tumor cells identified in histological preparations. Smaller increases (3-fold) in the Ly-2+ subset were also noted in the spleen and contralateral node, but they were seen later (7 to 8 weeks) and were shorter in duration. These systemic increases coincided with the appearance of macroscopic tumor nodules. The relative incidence of immunoglobulin+ cells did not change significantly in any of the organs tested during the entire tumor induction phase, while the level of null cells underwent a slight increase (approximately 2-fold) in all organs tested immediately prior to and following the appearance of macroscopic tumors. None of these changes was observed in trioctanoin oil-injected control animals. The mixed lymphocyte reaction response of the draining node cells, but not of the spleen, was suppressed during the period of increased level of Ly-2+ cells. Furthermore, during this period, s.c. transplantation of a syngeneic mammary tumor in the same leg resulted in enhanced local growth as well as metastatic spread of the tumor to the lungs in 3-methylcholanthrene-treated mice. These findings suggest that a localized immunosuppression associated with the rise in the Ly-2+ cells may be of functional significance during carcinogen-induced tumor development.