Expression of high-affinity IL-4 receptors on murine tumour infiltrating lymphocytes and their up-regulation by IL-2.
Since interleukin-2 (IL-2) and IL-4 act in concert to support the development of cytotoxic T lymphocytes (CTL) and the generation of antigen-specific tumour infiltrating lymphocytes (TIL), we investigated the interaction of these cytokines with an established TIL line. TIL proliferated in an additive fashion in response to suboptimal concentrations of IL-2 and various concentrations of IL-4. TIL possessed high-affinity IL-4 receptors whether cultured in recombinant IL-2 (rIL-2) or rIL-4, but cells cultured in rIL-2 had higher numbers of IL-4 receptors than cells cultured in rIL-4. When TIL were cultured in increasing concentrations of rIL-2, a dose-dependent enhancement in IL-4 receptor number was observed. The maximum induction of IL-4 receptor expression was achieved by 4 hr of incubation with rIL-2 and was completely blocked by cycloheximide. Other cytokines, such as rIL-1, recombinant tumour necrosis factor (rTNF), recombinant interferon-alpha (rIFN-alpha) and rIFN-gamma, had no effect on IL-4 receptor number. rIL-2 also up-regulated IL-4 receptors on CTLL-2, a murine CTL line. These data indicate that high-affinity IL-4 receptors exist on murine TIL and they can be up-regulated by IL-2. Our observation that IL-2 up-regulates IL-4 receptor may help explain the additive effects of these lymphokines on the proliferation of TIL and other cell lines. It may also help explain their co-operative effects on the generation of antigen-specific TIL and the differentiation of CTL.
Division of Cytokine Biology, CBER/FDA, Bethesda, MD 20892.
R K
RK
Puri
D S
DS
Finbloom
P
P
Leland
H
H
Mostowski
J P
JP
Siegel
D000818:Animals; D001685:Biological Factors / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D016207:Cytokines; D007376:Interleukin-2 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology*; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000032:analysis*; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology
D001685:Biological Factors; D016207:Cytokines; D007376:Interleukin-2; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D011994:Recombinant Proteins; D015847:Interleukin-4