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 Prepublished online as a Blood First Edition Paper on May 15, 2003; DOI 10.1182/blood-2002-11-3586.

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Blood, 1 September 2003, Vol. 102, No. 5, pp. 1764-1770

IMMUNOBIOLOGY

Rapid recovery from T lymphopenia by CD28 superagonist therapy

Karin Elflein, Marta Rodriguez-Palmero, Thomas Kerkau, and Thomas Hünig

From the Institute of Virology and Immunobiology, University of Würzburg, Würzburg, Germany.

Slow recovery of T-cell numbers and function contributes to the high incidence of life-threatening infections after cytotoxic cancer therapies. We have tested the therapeutic potential of a novel class of superagonistic CD28–specific antibodies that induce polyclonal T-cell proliferation without T-cell receptor engagement in an experimental rat model of T lymphopenia. We show that in lethally irradiated, bone marrow–reconstituted hosts, CD28 superagonist is able to dramatically accelerate repopulation by a small inoculum of mature, allotype-marked T cells. CD28-driven recovery of CD4 cells was superior to that of CD8 T cells. CD28 superagonist– expanded CD4 T cells had maintained repertoire diversity and were functional both in vitro and in vivo, suggesting that treatment with a human CD28–specific superagonist will protect T-lymphopenic patients from opportunistic infections.


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