Rapid recovery from T lymphopenia by CD28 superagonist therapy.
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.
Institute of Virology and Immunobiology, University of Würzburg, Versbacher Strasse 7, 97078 Würzburg, Germany. huenig@vim.uni-wuerzburg.de
Karin
K
Elflein
Marta
M
Rodriguez-Palmero
Thomas
T
Kerkau
Thomas
T
Hünig
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018106:CD28 Antigens / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D004195:Disease Models, Animal; D007167:Immunotherapy; D066298:In Vitro Techniques; D008231:Lymphopenia / Q000628:therapy*; D008934:Mitogens / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000166:cytology* / Q000637:transplantation; D013934:Thymectomy
D000906:Antibodies; D018106:CD28 Antigens; D008934:Mitogens