Article

Rapid recovery from T lymphopenia by CD28 superagonist therapy.

Institute of Virology and Immunobiology, University of Würzburg, Versbacher Strasse 7, 97078 Würzburg, Germany.
Blood (impact factor: 9.9). 10/2003; 102(5):1764-70. DOI:10.1182/blood-2002-11-3586 pp.1764-70
Source: PubMed

ABSTRACT 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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Keywords

allotype-marked T cells
 
bone marrow-reconstituted hosts
 
CD28 superagonist-
 
CD4 cells
 
CD4 T cells
 
CD8 T cells
 
cytotoxic cancer therapies
 
experimental rat model
 
human CD28-specific superagonist
 
induce polyclonal T-cell proliferation
 
lethally irradiated
 
mature
 
opportunistic infections
 
repertoire diversity
 
repopulation
 
superagonistic CD28-specific antibodies
 
T lymphopenia
 
T-cell numbers
 
T-cell receptor engagement
 
therapeutic potential