CD27 and CD70 are members of the TNF receptor and TNF family, respectively. A key function of the TNF receptor family is the regulation of immune reactions. The best documented effect of the interaction between CD27 and CD70 is costimulation of human T-cell proliferation. To be able to follow and manipulate the contribution of the CD27/CD70 interaction in immune responses, we decided to study these molecules in the murine system. Initial tools were obtained by cloning of murine CD70 and the generation of monoclonal antibodies directed to murine CD70. Subsequently the expression of mCD70 on (in-vitro stimulated) mouse lymphocytes was analyzed and compared with the expression on human lymphocytes.
In the human system CD70 expression is exclusively found on primed B and T cells. In vitro, TCR and BCR crosslinking on unprimed cells results in CD70 induction. Costimulation by CD40, CD28, IL-12 and TNF-alpha upregulate CD70 expression, whereas IL-4 and IL-10 downregulate CD70 expression. In the murine system we were only able to detect CD70 on in vitro stimulated B cells. Stimulation of B cells with alpha-IgM, LPS or CD40 monoclonal antibody resulted in a gradual induction of CD70 expression. In some cases (dependent on the mouse strain used), a synergistic effect of CD40 and LPS could be seen. Addition of an array of cytokines to mouse B-cell cultures only resulted in a change of CD70 expression in the case of IL-10, which decreased CD70 expression.
Although the absence of CD70 expression on mouse T cells is in agreement with results found by others, CD70 mRNA can be found in concanavalin-A-stimulated thymocytes. These contradicting results imply the possibility that CD70 is expressed on mouse T cells and subsequently cleaved off by a metalloprotease, as is shown for other TNF family members. A more careful comparison of CD70 mRNA and protein expression will solve this matter. |
