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Nonoverlapping Expression of IL10, IL12p40, and IFN mRNA in the Marginal Zone and T Cell Zone of the Spleen after Antigenic Stimulation¹

Kathrin Kalies^2,*, Peter König^*, Yong-Ming Zhang^*,, Maria Deierling^*, Julia Barthelmann^*, Claudia Stamm^* and Jürgen Westermann^*

^* Centre for Structural and Cell Biology in Medicine, Institute of Anatomy, University of Luebeck, Luebeck, Germany; and Department of Ophthalmology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China

The differentiation of CD4⁺ T cells is regulated by cytokines locally within the compartments of secondary lymphoid organs during adaptive immune responses. Quantitative data about the expression of cytokine mRNAs within the T and B cell zones of lymphoid organs are lacking. In this study, we assessed the expression of multiple cytokine genes within the lymphoid compartments of the spleen of rats after two types of stimulation. First, the spleen was stimulated directly by a blood-derived Ag. Second, the spleen was stimulated indirectly by incoming lymphocytes that had been activated and released during a proceeding immune response at a distant tissue site. Using laser microdissection, we show that the expression of cytokine mRNAs was compartment specific, transient, and preceded cell proliferation after the direct antigenic stimulation. Surprisingly, the indirect stimulation by incoming activated lymphocytes induced similar cytokines in the T cell zone. However, the nonoverlapping expression was lost and IL10 appeared as the major cytokine in all compartments. Thus, tracking two types of immune activation without disturbing the integrity of structures reveals distinct and overlapping events in the compartments of the spleen. This information adds a new dimension to the understanding of immune responses in vivo.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by German Research Foundation Grant SFB 654-C4.

² Address correspondence and reprint requests to Dr. Kathrin Kalies, Institute of Anatomy, University of Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany. E-mail address: kalies{at}anat.uni-luebeck.de

³ Abbreviations used in this paper: MZ, marginal zone; ct, cycle of threshold; TCZ, T cell zone; BCF, B cell follicle; DC, dendritic cells; RP, red pulp; GC, germinal center.