IL-2, IL-10, IL-15 and TNF are key regulators of murine T-cell lymphoma growth.
We studied the role of IL-2, IL-15, IL-10, TNF and IL-2 receptor complexes (IL-2R) produced constitutively by a T-cell lymphoma line (LBC) on their own proliferation. The constitutive expression of surface alpha, beta and gamma chains IL-2R was detected in tumor cells by flow cytometry. Using reverse-transcription PCR, mRNA for IL-2, IL-15, IL-10 and TNF were found to be present in LBC. In addition, tumor cells were found to constitutively express intracellular IL-2, IL-15, IL-10 and TNF. Despite the production of these cytokines by tumor cells, specific neutralising antibodies did not inhibit LBC proliferation; surprisingly, anti-IL-15 increased LBC cell growth. We also demonstrated that recombinant IL-2 or IL-15 enhanced LBC cell proliferation. Our data suggest that endogenous IL-2 and IL-15 may trigger the proliferation of lymphoma LBC cells, and so their growth could be regulated, at least partly, by IL-2/IL-15/IL-2R system. In addition, IL-10 and TNF, immunosuppressor and pro-metastatic cytokines, respectively, may promote the in vivo growth of the tumor. The fact that leukaemia-lymphoma cells produce simultaneously both IL-2 and IL-15 should be taken into consideration in the design of immunotherapy protocols directed to IL-2R.
Gravisaco
María José
MJ
Centro de Estudios Farmacológicos y Botánicos (CEFYBO), CONICET, Serrano 669, Buenos Aires 1414, Argentina. majo@interserver.com.ar
Mongini
Claudia
C
Alvarez
Elida
E
Ruybal
Paula
P
Escalada
Ana
A
Sanchez-Lockhart
Mariano
M
Hajos
Silvia
S
Waldner
Claudia
C
D000818:Animals; D002455:Cell Division; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D016753:Interleukin-10 / Q000502:physiology*; D019409:Interleukin-15 / Q000502:physiology*; D007376:Interleukin-2 / Q000502:physiology*; D016399:Lymphoma, T-Cell / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D016207:Cytokines; D019409:Interleukin-15; D007376:Interleukin-2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10