Submitted November 27, 2002
Accepted April 21, 2003
Rapid recovery from T lymphopenia by CD28 superagonist therapy
Karin Elflein, Marta Rodriguez-Palmero, Thomas Kerkau, and Thomas Huenig*
Institute for Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany
* Corresponding author; email: huenig{at}vim.uni-wuerzburg.de.
Slow recovery of T-cell numbers and function contributes to the high incidence in life-threatening infections after cytotoxic cancer therapies. We have tested the therapeutic potential of a novel class of superagonistic CD28 specific antibodies which 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.
