Helper T Cell Anergy

It has been shown that agonistic anti-CD137 mAbs are potent suppressors of T cell-dependent humoral immunity (Mittler et al., 1999). When naïve B cells were adoptively transferred into SCID recipient mice together with T cells, which were isolated from mice immunized with SRBC and treated with agonistic anti-CD137 mAb, the recipients generated deficit anti-SRBC humoral responses. However, when naïve T cells were adoptively transferred into SCID recipients along with B cells, which were isolated from SRBC-immunized and anti-CD137-treated mice, the recipients developed normal humoral responses to SRBC (Mittler etal., 1999). These experiments indicate CD137 engagement in vivo with agonist antibodies preclude the generation of functional helper T cell populations.

Agonistic anti-CD137 treatment of NZB x NZW F1 mice did not induce massive depletion of lymphocytes including CD4+ T cells as in MRL/lpr mice. And anti-CD137 mediated disease blockade is not CD8+ T cell dependent (Foell et al., 2003). These suggest other mechanisms than increased AICD of CD4+ T cells and induction of CD8+ regulatory T cells may be involved. Administration of anti-CD137 inhibited IL-2 and IL-4 production by CD4+ T cells, and adoptive transfer of antigen-primed CD4+ T cells isolated from untreated mice or bone marrow-derived dendritic cells (DCs) reversed CD137-mediated disease protection in NZB x NZW F1 mice. These data imply CD137-mediated signaling may anergize CD4+ T cells (Foell et al., 2003; Mittler et al., 1999).

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