Certain T cell subsets are able to survive depletion under immunosuppression, can become potent alloreactive memory T cells, causing allograft injury. CD30 is expressed on activated T and B cells. It was shown that allostimulation induces CD30 expression and increases the release of soluble CD30 by memory T cells. Furthermore, generation of memory Th1 and Th17 seems to depend on induction of Transglutaminase 2-expression via CD30.

We investigated whether blocking of the CD30-CD30 ligand (CD153) pathway in a mixed lymphocyte culture might lead to inhibition of T cell proliferation.

Tested responder lymphocytes from a healthy blood donor were stimulated by a pool of HLA-DRB1-mismatched cells. After addition of different antibodies against CD30 and CD30 ligand, the cells were incubated for seven days at 37°C. Afterwards, proliferating T cell blasts were acquired with flow cytometry. The same experiment was performed with brentuximab vedotin (an antibody-drug-conjugate) and several immunosuppressive drugs to examine a possibly synergistic inhibitory effect.

With the exception of brentuximab vedotin and high dosages of immunosuppressive drugs, none of the unconjugated anti-CD30 and anti-CD30-ligand antibodies showed an effect in vitro on the T cell proliferation when added alone or in combination. Brentuximab vedotin alone failed to impact the number of CD30+/CD45RO+ memory T cells and its addition to immunosuppressive drugs did not demonstrate a consistent synergistic effect.

Unconjugated antibodies directed at CD30 or CD30L are not powerful enough to influence T cell proliferation in vitro. Conjugation with a toxin has an impact on proliferation of CD30+ T cells, but not specifically on the CD30+ memory T cell subset. This observation suggests that allogeneic T cell activation cannot be blocked via only one expressed surface molecule and that specific depletion of memory T cells may require more than one cellular target.

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