Responses to T cell receptor/CD3 and interleukin-2 receptor stimulation are altered in T cells from B cell non-Hodgkin's 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, 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.
Kudoh
S
S
Department of Immunology, Cleveland Clinic Foundation, Ohio 44195, USA.
Wang
Q
Q
Hidalgo
O F
OF
Rayman
P
P
Tubbs
R R
RR
Edinger
M G
MG
Kolenko
V
V
Panuto
J
J
Bukowski
R
R
Finke
J H
JH
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007376:Interleukin-2; D007476:Ionophores; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D014443:Tyrosine; D015759:Ionomycin; D007371:Interferon-gamma