Relationship between T lymphocyte levels and lymphoproliferative responses to mitogens and alloantigens in lung and breast cancer patients

Abstract

AbstractLung and breast cancer patients were studied for relationships between lymphocyte function, as measured by lymphoproliferative (LP)3 assays, and levels of circulating thymus‐derived lymphocytes (T lymphocytes) measured by rosette formation with sheep erythrocytes (E rosettes). LP responses to the T lymphocyte mitogens phytohemagglutinin (PHA) and concanavalin‐A (Con‐A) and to alloan‐tigens in one‐way mixed leukocyte cultures (MLC) were assessed in a microculture assay. Total T lymphocyte levels were determined using an E rosette assay performed at 4°C and a subpopulation of T lymphocytes with high affinity receptors for E rosettes was measured in a 29°C assay. Using the relative proliferation index (RPI) which compares patient reactivity to normal reactivity, we found that one‐third to one‐half of the lung and breast cancer patients had depressed LP responses to at least one of the stimulants. In contrast, only 21% of the breast and 25% of the lung cancer patients had low levels of total E‐rosette‐forming cells (E‐RFC) as measured by the 4°C E rosette assay. Using the 29°C E rosette assay, we found that a significantly higher proportion of the patients demonstrated decreased levels of this subpopulation of lymphocytes and in both patient groups the depression noted in functional assays was closely paralleled by the percentage of patients with abnormal levels of high‐affinity T lymphocytes. To further examine this apparent relationship between high‐affinity E‐RFC levels and LP results, the correlation between these measures in individual patients was examined. Regression analysis indicated a significant correlation between mitogen and alloantigen responses in both patient groups as well as between total T lymphocyte and high‐affinity T lymphocyte levels. However, there was no significant correlation between LP responses and T lymphocyte levels. Studies in which MLC and PHA reactivities, 4°C and 29°C E rosette levels were determined on the same peripheral blood leukocyte (PBL) sample demonstrated that a number of lung and breast cancer patients with abnormal LP responses had normal total and high‐affinity T lymphocyte levels. Patients with a decrease in high‐affinity E‐RFC but normal levels of total T lymphocytes had a high incidence of depression to PHA (56 and 82% in breast and lung cancer patients respectively) but fewer had depressed MLC reactivity (33 and 71% in breast and lung cancer patients, respectively). In patients with low levels of total and high‐affinity T lymphocytes, there was a high incidence of depression in responses to both PHA and MLC. The results of this study indicate that some cancer patients may have depressed LP responses in association with depressed levels of T lymphocytes, but that other patients may have depressed functional reactivity despite normal levels of E‐RFC.