Responses to T cell receptor/CD3 and interleukin-2 receptor stimulation are altered in T cells from B cell non-hodgkin's lymphomas

Abstract

T cells infiltrating (T-TIL) B cell non-Hodgkin's lymphomas (NHL) are thought to represent a local host response to the tumor. However, tumor progression in the presence of this T cell infiltrate suggests that the T-TIL may be functionally impaired. To address this issue we determined 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 important for proliferation and cytokine production. Our results demonstrate 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 stimulation through the TCR/CD3 complex did not induce mRNA for interferon gamma (IFN gamma), IL-2, IL-4 or IL-10. The functional unresponsiveness of these cells may be linked to altered signalling through the TCR/CD3 since an abnormal tyrosine phosphorylation pattern was detected in T-TIL after stimulation with anti-CD3.

Attenuation of CD8+ T-Cell Function by CD4+CD25+ Regulatory T Cells in B-Cell Non-Hodgkin's Lymphoma

“…Previous studies have shown that lymphoma B cells are resistant to CTL-mediated cell death (3)(4)(5), and this has been attributed to changes in their genetic or protein expression profile (3-5, 13, 14) as well as to abnormal CTL function (15)(16)(17). Additionally, there is accumulating data suggesting that T reg cells are capable of inhibiting CD8 + T cells under different pathologic conditions such as infection (18,19) or allograft transplantation in vivo (20,21).…”