Partial restoration of local GVH reaction in cancer patients by depletion of theophylline-sensitive suppressor T-cells.
Theophylline-resistant T-cell subpopulations were assessed in terms of numbers and function among patients with disseminated cancer, and compared to normal controls. Within the total E-rosetting T-cells (65 +/- 6.5% for normal donors versus 34 +/- 1.0% for cancer patients; P less than 0.001) the proportion of theophylline-resistant Te cells was 56 +/- 1.5% and 26.6 +/- 1.1%, respectively (P less than 0.001). This significant difference in distribution between theophylline-resistant (effector) and theophylline-sensitive (suppressor) cells in favor of the latter was also reflected by the poor performance of unseparated T-cells in the local GVH reaction. Thus, the mean GVH reaction among normal donors was 159 +/- 30 mm3 versus 44 +/- 28 mm3 among cancer patients (P less than 0.001). Removal of the theophylline-sensitive suppressor T-cells resulted in significant augmentation of the local GVH reaction among normal donors and in significant, although partial, immune restoration of the local GVH reaction in some patients but not in others. The mean local GVH reaction after removal of theophylline-sensitive suppressor T-cells was 196 +/- 89 mm3 among normal donors and 68 +/- 46 mm3 among cancer patients (P less than 0.05). This immune restoration following depletion of suppressor T-cells was only partial among cancer patients because of an apparent intrinsic defect in the capacity of their effector T-cells to exert vigorous local GVH reaction. In one small group of four patients, this intrinsic defect was so profound that even after removal of the theophylline-sensitive suppressor cells, the restoration of the local GVH reaction was negligible (12 +/- 10.8 mm3 versus 24 +/- 9.8 mm3; P greater than 0.1). The quantitative and qualitative changes in effector and suppressor T-cell distribution during the development of the malignant process and the possible interaction between them are discussed.
D000818:Animals; D002469:Cell Separation; D006087:Graft vs Host Reaction; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D009369:Neoplasms / Q000276:immunology*; D011336:Probability; D051381:Rats; D011917:Rats, Inbred Lew; D012397:Rosette Formation; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013806:Theophylline / Q000494:pharmacology
D013806:Theophylline