In vivo and in vitro growth of murine B cell lymphoma (BCL1): I; regulation of interleuk-in4 and interleuk-in5 production by murine T cells and II growth of an IL5 responsive lymphoma is not T cell dependent
Creators: name: Diegel, Michael Lee
Publisher: name: University of Utah
Year: 2012
Subjects: T Cells
Growth and Developoment

description: The lymphokines (interieukins) IL-4 and IL-5 are important regulatory elements of the immune system and are able to synergize with each other in regulating B cell maturation and differentiation. Thus, many studies have proposed a common in vivo and in vitro regulation of IL~4 and IL-5 production by mitogen or antigen activated T cells. Results reported here indicate a similar distribution of IL-4 and IL-5 production by T cells isolated from a variety of lymphoid organs in both aged and young mice. IL-4 and IL-5 production by activated T ceUs is similarly enhanced in aged mice (74 weeks old) within the mucosal lymph node (MLN), peripheral lymph node (PLN) and spleen compared to adult mice (15 weeks old). Our laboratory has observed that selected endogenous steroids are capable of altering the lymphokine-producing potential of activated T cells; the effect of some of these steroids is to elicit a lymphokine profile similar to that produced by T cells isolated from different lymphoid tissues. To further address the apparent coordinated regulation of IL-4 and IL-5 production, T cells were pulsed with either dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT), glucocorticosterone (GCS), or 1,25 dihydroxyvitamin D3 (l,25(OH)2D3). Murine activated T cells and T cell clones exposed to the active form of Vitamin D3, l,25(OH)2D3, upregulated secretion of IL-4 and IL-5. However DHT, the active form of the androgen testosterone, reduced IL-4 and IL-5 production by anti-CD3 activated T ceUs. DHEA, which has been shown to upregulate IL-2 secretion by murine activated T cells, had no effect on IL-4 or 11-5 production. Similar regulation of IL-4 and 11-5 has important implications for augmenting the humoral arm of the immune response. The results presented herein indicate that naturally produced steroids have regulatory influences on these lymphokines and that steroids may also be important controlling elements of immune regulation.  The murine BCL1 lymphoma has been described as the murine correlative to human chronic lymphocytic leukemia. It may be an important tumor model for understanding tumor growth and how transformation occurs. This tumor cell line has been well recognized as responsive, at least in the short term, to the lymphokines IL-4 and IL-5 in vitro. These lymphokines are T cell products which have been shown to contribute to regulation of humoral immunity and may also be important to maintenance and growth of BCL1 in vivo. To investigate this hypothesis, three approaches were used to obtain a T cell deficient experimental system: Nude mice, thymectimized/gamma irradiated mice (ATXBM), and in vivo antibody-mediated CD4 and CDS depletions. The last model was most effective where Balb/c mice were depleted of CD4+ and CDS+ T cells by injection of monoclonal antibody before and after injection of BCLi tumor. Tumor growth was examined by ability to palpate the spleen, spleen weight, splenic gross examination, histochemical staining, and flow cytometry. Results indicated that neither CD4+ or CDS+ cells contributed significantly to the transplantability or tumorigenicity of murine BCL1i lymphoma. BCL1 apparently proliferated with increased rate of growth, as evaluated by tumor mass, in the absence of T cells.