Rapid Recovery From T Lymphopenia Using CD28 Agonist

[Guest guest]

Blood First Edition Paper

prepublished online May 15, 2003

Submitted November 27, 2002

Accepted April 21, 2003

Rapid recovery from T lymphopenia by CD28 superagonist therapy

Karin Elflein, Marta -Palmero, Kerkau, and

Huenig*

Institute for Virology and Immunobiology, University of Wuerzburg,

Wuerzburg, Germany

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.