The effect of exogenous/endogenous TNF therapy on the subsets of peripheral blood lymphocytes

Decrease of DAF- cells among CD8⁺ lymphocytes after TNF-S injection

Abstract

We have demonstrated that exogenous/endogenous TNF therapy (EET therapy) is efficient for advanced colorectal cancers. This therapy is based on the idea that endogenous TNF is induced in the serum of most cancer patients when treated firstly with recombinant TNF-S_AM2 (TNF-S) followed by administration of OK-432. We evaluated the changes in the counts of peripheral blood lymphocytes (PBL) and its subsets especially CD 8⁺DAF^- lymphocytes, of ten colorectal cancers patients who had received EET therapy. We examined them 2 hours after infusion of TNF-S as the primer, and then 4 and 24 hours after injection of OK-432 as the trigger. Band-form neutrophil counts increased remarkably after TNF-S infusion and even more after OK-432 injection. WBC, PBL, monocytes, CD 16⁺ cells, CD 8⁺CD 11 b^- lymphocytes and CD 8⁺DAF^- lymphocytes, however, tended to decrease after TNF-S infusion and recover within several days after OK-432 injection. CD 4/CD 8 ratio kept a higher level for 24 hours due to the decrease of CD 8⁺ lymphocytes. CD 8⁺DAF^- lymphocytes, to which we paid special attention as activated T cells, decreased rapidly to below 3% in 60 minutes after TNF-S infusion. CD 16⁺ cells and CD 14⁺ cells showed the same pattern as CD 8⁺DAF^- cells.
However CD 8⁺DAF^- lymphocytes did not decrease in vitro when treated with TNF-S or with serum obtained from a patient treated with TNF-S. Therefore, the decrease of CD 8⁺ DAF^- lymphocytes in peripheral blood might not be due to the down regulation of DAF expression by TNF itself or some TNF-induced cytokines. The temporary decrease of cells related to immunological activities, such as CD 8⁺DAF^- lymphocytes by TNF-S, could be due to them becoming trapped in cancer lesions, lymphoid organs or capillaly walls. The reason for the latter is, as yet, unknown.