RESPONSES TO T-CELL RECEPTOR CD3 AND INTERLEUKIN-2 RECEPTOR STIMULATION ARE ALTERED IN T-CELLS FROM B-CELL NON-HODGKINS-LYMPHOMAS

T cells infiltrating (T-TIL) B cell non-Hodgkin's lymphomas (NHL) are thought to represent a local host response to the tumor. However, tumo r progression in the presence of this T cell infiltrate suggests that the T-TIT, may be functionally impaired. To address this issue we dete rmined whether response to stimulation of T-TIL from 25 patients with NHL through the T cell receptor (TCR/CD3) and the interleukin-2 (IL-2) receptor (IL-2R) was intact, since activation of these receptors is i mportant for proliferation and cytokine production. Our results demons trate defects in response to stimulation via TCR/CD3 and the IL-2R in T-TIL cells from patients with NHL that were not observed with T cells from the peripheral blood. T-TIL showed minimal proliferation to anti -CD3 and only modest proliferation to IL-2 alone or when combined with anti-CD3. Moreover, cytokine production in T-TIL was impaired since s timulation through the TCR/CD3 complex did not induce mRNA for interfe ron gamma (IFN gamma), IL-2, IL-4 or IL-10. The functional unresponsiv eness of these cells may be linked to altered signalling through the T CR/CD3 since an abnormal tyrosine phosphorylation pattern was detected in T-TIL after stimulation with anti-CD3.