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Recombinant human IL‐7 (rhIL‐7) preferentially expands CD4+ and CD8+ naïve T cells and enhances T cell receptor (TCR) repertoire diversity
Author(s) -
Sportes Claude,
Hakim Frances T,
Memon Sarfraz A,
Zhang Hua,
Brown Margaret R,
Fleisher Thomas A,
Krumlauf Michael C,
Babb Rebecca R,
Chow Catherine K,
Fry Terry J,
Engels Julie,
Buffet Renaud,
Morre Michel,
Venzon David J,
Korngold Robert,
Pecora Andrew,
Mackall Crystal L,
Gress Ronald E
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1070.6
Subject(s) - cd8 , t cell receptor , biology , immunology , t cell , cytotoxic t cell , receptor , immune system , in vitro , biochemistry
Aging is associated with a decline in T cell generation and TCR repertoire diversity and a progressive accumulation of oligoclonal, terminally differentiated and functionally limited CD8 + effector T cells which may impede new responses. A phase I study of rhIL‐7 (subcutaneously every other day for 2 weeks) evaluated toxicity and biologic activity in 16 adults (age 20–71). RhIL‐7 was well tolerated. It resulted in a dose but not age dependent preferential expansion of naïve CD8 + T cells and of CD4 + RTEs, naïve and central memory T cells. (4 to 5‐fold at the higher doses of 30 and 60 μg/Kg/dose). T cells remained functional in vitro and persisted for 6–8 weeks. The naïve T cell expansions resulted in increased TCR diversity assessed before and one week after treatment. We scored divergence between each Vβ spectratype and normal standard comparing all the pre and post scores by Wilcoxon paired test. The increase in diversity was statistically significant in 4 of 6 subjects in CD4 + , CD8 + or both. RhIL‐7 resulted in circulating T‐cell profiles resembling what is seen early in life with abundant naïve T‐cells and wide TCR diversity. We propose that rhIL‐7 has the potential of becoming a clinically usable T‐cell growth factor for rejuvenation of peripheral T‐cell populations in hosts with impaired immunity due to physiologic (age), iatrogenic (chemotherapy) or pathologic (HIV) lymphodepletion.