The Journal of Immunology, Vol 154, Issue 2 718-729, Copyright © 1995 by American Association of Immunologists

ARTICLES

Lymphokine mRNA expression by transplantable murine B lymphocytic malignancies. Tumor-derived IL-10 as a possible mechanism for modulating the anti-tumor response

KL Bost, SC Bieligk and BM Jaffe
Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112.

In vitro and in vivo expressions of cytokine mRNAs by four transplantable murine B lymphocytic malignancies designated A20, MOPC 315, 2PK-3, and RAW 8.1 were determined using sensitive reverse- transcribed (RT)-PCR. Despite significant differences in both the stage of B cell differentiation represented by each cell line and the method used to induce the original B lymphocytic tumors, IL-6 and IL-10 mRNAs were detected in each of the cultured cell lines. Whereas IL-2, IL-4, IL-5, and IL-12 mRNAs were not detected in cultured cells, expression of cytokine mRNAs in solid tumor tissue was quite different. RT-PCR of poly(A)+ RNA isolated from each of the four solid tumors demonstrated the presence of IL-4, IL-5, IL-6, IL-10, TGF-beta 1, and TNF-alpha mRNAs. There was a noticeable lack of significant IL-2 mRNA expression in any of the solid tumors. Using RT-PCR, it was clear that each of the malignant B lymphocytes expressed IL-6, IL-10, TGF-beta 1, and TNF- alpha, with limited expression of IL-4 and IL-5. To explore the mechanisms that might contribute to the lack of IL-2 mRNA in these solid tumors, quantitative competitive (QC)-RT-PCR was used to quantify expression of IL-10 mRNA. MOPC 315 tumor expressed the most IL-10 mRNA (23.2 pg/micrograms of poly(A)+ RNA), whereas 2PK-3, A20, and RAW 8.1 tumors expressed 7.4, 2.6, and 0.6 pg/micrograms of poly(A)+ RNA, respectively. Secretion of IL-10 into culture supernatants or into sera and ascitic fluid of tumor-bearing animals correlated with mRNA expression. This dysregulated IL-10 production in animals with B lymphocytic tumors suggested a mechanism that may account for the lack of IL-2 mRNA expression in solid tumors, and suggested a possible mechanism by which malignant B lymphocytes may limit cell-mediated antitumor responses.

This article has been cited by other articles:

				N. Gasper-Smith, I. Marriott, and K. L. Bost Murine {gamma}-Herpesvirus 68 Limits Naturally Occurring CD4+CD25+ T Regulatory Cell Activity following Infection J. Immunol., October 1, 2006; 177(7): 4670 - 4678. [Abstract] [Full Text] [PDF]

				S. Olver, P. Groves, K. Buttigieg, E. S. Morris, M. L. Janas, A. Kelso, and N. Kienzle Tumor-Derived Interleukin-4 Reduces Tumor Clearance and Deviates the Cytokine and Granzyme Profile of Tumor-Induced CD8+ T Cells Cancer Res., January 1, 2006; 66(1): 571 - 580. [Abstract] [Full Text] [PDF]

				M. Stassen, H. Jonuleit, C. Muller, M. Klein, C. Richter, T. Bopp, S. Schmitt, and E. Schmitt Differential Regulatory Capacity of CD25+ T Regulatory Cells and Preactivated CD25+ T Regulatory Cells on Development, Functional Activation, and Proliferation of Th2 Cells J. Immunol., July 1, 2004; 173(1): 267 - 274. [Abstract] [Full Text] [PDF]

				R. D. Brown, B. Pope, A. Murray, W. Esdale, D. M. Sze, J. Gibson, P. J. Ho, D. Hart, and D. Joshua Dendritic cells from patients with myeloma are numerically normal but functionally defective as they fail to up-regulate CD80 (B7-1) expression after huCD40LT stimulation because of inhibition by transforming growth factor-beta 1 and interleukin-10 Blood, November 15, 2001; 98(10): 2992 - 2998. [Abstract] [Full Text] [PDF]

				T. Portis, J. C. Harding, and L. Ratner The contribution of NF-{kappa}B activity to spontaneous proliferation and resistance to apoptosis in human T-cell leukemia virus type 1 Tax-induced tumors Blood, August 15, 2001; 98(4): 1200 - 1208. [Abstract] [Full Text] [PDF]

				A. Elhofy, I. Marriott, and K. L. Bost Salmonella Infection Does Not Increase Expression and Activity of the High Affinity IL-12 Receptor J. Immunol., September 15, 2000; 165(6): 3324 - 3332. [Abstract] [Full Text] [PDF]

				J. W. Peacock and K. L. Bost Infection of intestinal epithelial cells and development of systemic disease following gastric instillation of murine gammaherpesvirus-68 J. Gen. Virol., February 1, 2000; 81(2): 421 - 429. [Abstract] [Full Text]

				A. Elhofy and K. L. Bost Limited Interleukin-18 Response in Salmonella-Infected Murine Macrophages and in Salmonella-Infected Mice Infect. Immun., October 1, 1999; 67(10): 5021 - 5026. [Abstract] [Full Text] [PDF]

				K. R. WALLEY, T. E. MCDONALD, Y. HIGASHIMOTO, and S. HAYASHI Modulation of Proinflammatory Cytokines by Nitric Oxide in Murine Acute Lung Injury Am. J. Respir. Crit. Care Med., August 1, 1999; 160(2): 698 - 704. [Abstract] [Full Text]

				J. W. Rohrer, A. L. Barsoum, D. L. Dyess, J. A. Tucker, and J. H. Coggin Jr. Human Breast Carcinoma Patients Develop Clonable Oncofetal Antigen-Specific Effector and Regulatory T Lymphocytes J. Immunol., June 1, 1999; 162(11): 6880 - 6892. [Abstract] [Full Text] [PDF]

				J.-P. Zou, L. A. Morford, C. Chougnet, A. R. Dix, A. G. Brooks, N. Torres, J. D. Shuman, J. E. Coligan, W. H. Brooks, T. L. Roszman, et al. Human Glioma-Induced Immunosuppression Involves Soluble Factor(s) That Alters Monocyte Cytokine Profile and Surface Markers J. Immunol., April 15, 1999; 162(8): 4882 - 4892. [Abstract] [Full Text] [PDF]

				K. Lingnau, P. Hoehn, S. Kerdine, S. Koelsch, C. Neudoerfl, N. Palm, E. Ruede, and E. Schmitt IL-4 in Combination with TGF-{beta} Favors an Alternative Pathway of Th1 Development Independent of IL-12 J. Immunol., November 1, 1998; 161(9): 4709 - 4718. [Abstract] [Full Text] [PDF]

				Y. Okura, K. Takeda, S. Honda, H. Hanawa, H. Watanabe, M. Kodama, T. Izumi, Y. Aizawa, S. Seki, and T. Abo Recombinant Murine Interleukin-12 Facilitates Induction of Cardiac Myosin–Specific Type 1 Helper T Cells in Rats Circ. Res., June 1, 1998; 82(10): 1035 - 1042. [Abstract] [Full Text] [PDF]

				P. P. Lee, D. Zeng, A. E. McCaulay, Y.-F. Chen, C. Geiler, D. T. Umetsu, and N. J. Chao T Helper 2-Dominant Antilymphoma Immune Response Is Associated With Fatal Outcome Blood, August 15, 1997; 90(4): 1611 - 1617. [Abstract] [Full Text] [PDF]