International Immunology, Vol. 7, No. 3, pp. 381-392,March 1995
© 1995 Japanese Society for Immunology
Induction of CD5 on B and T cells is suppressed by cyclosporin A, FK-520 and rapamycin
Department of Pathology, Tufts University School of Medicine Boston, MA 02111, USA
1 Division of Tumor Virology, Dana Farber Cancer Institute and the Department of Pathology, Harvard Medical School Boston, MA 02115, USA
Correspondence to: Correspondence to: H. Wortis
The expression of CD5 can be induced on murine B-2 cells by anti-IgM, a recognized analog of thymus-independent 2 type (TI-2) antigen. Given that cyclosporin A (CsA) sensitivity is a distinguishing feature of TI-2 type B cell activation, we asked whether the in vitro induction of CD5 on B cells by anti-µ is CsA sensitive. We report that anti-µ induced CD5 expression on B-2 cells was inhibited by CsA as well as FK-520 and rapamycin. When L-685,818, a FK-520 and rapamycin antagonist, was added to anti-µ stimulated B cell cultures containing FK-520 or rapamycin, but not CsA, suppression was abrogated and complete induction of CD5 was seen. When we used either CD4+CD8+ thymocytes or peripheral T cells activated by phorbol ester and ionomycin, the cell surface induction of CD5 was also partially blocked by CsA, FK-520 and rapamycin. Moreover, in both B and T cells, the same immunosuppressive drugs did not affect constitutive CD5 expression but only blocked de novo induction. To determine the level of CD5 regulation, we activated T cells using phorbol myristate acetate (PMA)/ionomycin and report that CD5 induction was sensitive to actinomycin D (AcD). Similarly, the induction of CD5 on anti-µ activated B cells was blocked by AcD. In addition, T cells that were activated by PMA/ionomycin expressed more abundant CD5 mRNA than CsA or FK-520 treated cells. Based on the CsA-sensitive regulation of CD5 we thought that the CsA-sensitive nuclear factor of activated T cells (NFAT) might be involved in CD5 regulation. We report evidence by Western blot analysis that NFATp is expressed by both resting and TI activated B cells but apparently not CD4+CD8+CD5+ thymocytes. We conclude that in both B and T cells the induction of CD5 requires transcriptional regulation, and that the inhibition of CD5 expression by the immunosuppressive drugs CsA, FK-520 and rapamycin requires drug-immunophilin complex formation.
Keywords: immunophilins, NFATp, thymus-independent2 type
Received 16 September 1994, accepted 16 November 1994.
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