Intracellular IL-4/IFN-gamma producing peripheral T lymphocyte subsets in B cell non-Hodgkin's lymphoma patients.
OBJECTIVE
The availability of several biological therapy options is rapidly growing in the field of malignant lymphomas. This emphasizes the need to understand the precise interaction of the host immune system with the malignant disease. We measured the intracellular cytokine responses in lymphoma patients' lymphocytes, to characterize the polarization changes in their immune system.


METHODS
Patients with B cell non-Hodgkin's lymphoma were involved in the study. Peripheral lymphocytes were labeled with anti-CD4 or anti-CD8 antibodies and intracellular accumulation of IL-4 or IFN-gamma was detected after in vitro incubation the cells with activating cocktail. The frequency of different T-cell subsets were measured within the lymphocyte population.


RESULTS
Significantly increased CD4+, IFN-gamma producing (Th1) cell percentage were found in untreated lymphoma cases (28.8% vs. 21.8%). CD8+ IL-4 and IFN-gamma producing (Tc0) T cell frequency is significantly higher in untreated lymphoma patients compared with normal controls (1.3% vs. 0.47%). The frequency of CD4+ IL-4 producing (Th2) cells is significantly lower in untreated patients (0.96% vs. 1.19%). Patients in long-term remission have lower frequency of CD4+, IL4 producing (Th2) cell ratio (0.31% vs. 1.19%) and increased CD4+ IFN-gamma producing (Th1) cell frequency (30.1% vs. 21.8%), compared with healthy normal controls.


CONCLUSIONS
Our results demonstrate that there is a sustained increase in the CD4+ IFN-gamma producing cell frequency in lymphoma patients. The frequency of CD4+ IL-4 producing cells is decreasing by treatment. These may contribute to strong polarization toward Th1 type response, needed for lymphoma clearance and remission.
Gergely
Lajos
L
Third Department of Internal Medicine, Institute of Internal Medicine, Medical and Health Science Center, University of Debrecen, PO Box 3, H-4004 Debrecen, Hungary. gergely@iiibel.dote.hu
Aleksza
Magdolna
M
Váróczy
László
L
Ponyi
Andrea
A
Sipka
Sándor
S
Illés
Arpád
A
Szegedi
Gyula
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001761:Bleomycin / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D007424:Intracellular Fluid / Q000378:metabolism; D018655:Lymphocyte Count; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage; D011241:Prednisone / Q000008:administration & dosage; D012074:Remission Induction; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D014750:Vincristine / Q000008:administration & dosage
D003561:Cytarabine; D001761:Bleomycin; D015847:Interleukin-4; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D007371:Interferon-gamma; D003520:Cyclophosphamide; D011239:Prednisolone; D011241:Prednisone; D008727:Methotrexate