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PMID: 7699326 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The effect of in vivo IL-7 deprivation on T cell maturation.

The Journal of experimental medicine ·Vol. 181 ·No. 4 ·1995-04-01 ·Pages 1399-409

Bhatia SK, Tygrett LT, Grabstein KH, Waldschmidt TJ

Abstract

A number of previous studies have suggested a key role for interleukin 7 (IL-7) in the maturation of T lymphocytes. To better assess the function of IL-7 in lymphopoiesis, we have deprived mice of IL-7 in vivo by long-term administration of a neutralizing anti-IL-7 antibody. In a previous report (Grabstein, K. H., T. J. Waldschmidt, F. D. Finkelman, B. W. Hess, A. R. Alpert, N. E. Boiani, A. E. Namen, and P. J. Morrissey. 1993. J. Exp. Med. 178:257-264), we used this system to demonstrate the critical role of IL-7 in B cell maturation. After a brief period of anti-IL-7 treatment, most of the pro-B cells and all of the pre-B and immature B cells were depleted from the bone marrow. In the present report, we have injected anti-IL-7 antibody for periods of up to 12 wk to determine the effect of in vivo IL-7 deprivation on the thymus. The results demonstrate a > 99% reduction in thymic cellularity after extended periods of antibody administration. Examination of thymic CD4- and CD8- defined subsets revealed that, on a proportional basis, the CD4+, CD8+ subset was most depleted, the CD4 and CD8 single positive cells remained essentially unchanged, and the CD4-, CD8- compartment actually increased to approximately 50% of the thymus. Further examination of the double negative thymocytes demonstrated that IL-7 deprivation did, indeed, deplete the CD3-, CD4-, CD8- precursors, with expansion of this subset being interupted at the CD44+, CD25+ stage. The proportional increase in the CD4-, CD8- compartment was found to be due to an accumulation of CD3+, T cell receptor alpha, beta + double negative T cells. Additional analysis revealed that anti-IL-7 treatment suppressed the audition/selection process of T cells, as shown by a significant reduction of single positive cells expressing CD69 and heat stable antigen. Finally, the effects of IL-7 deprivation on the thymus were found to be reversible, with a normal pattern of thymic subsets returning 4 wk after cessation of treatment. The present results thus indicate a central role for IL-7 in the maturation of thymic-derived T cells.

MeSH Terms
Animals Antibodies, Monoclonal/immunology,pharmacology Cell Differentiation Female Immunophenotyping Interleukin-7/antagonists & inhibitors,physiology Mice Mice, Inbred BALB C Specific Pathogen-Free Organisms T-Lymphocyte Subsets/cytology Thymus Gland/cytology Time Factors
Chemicals
Antibodies, Monoclonal Interleukin-7
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Bhatia S K
Department of Pathology, University of Iowa College of Medicine, Iowa City 52242, USA.
Tygrett L T
Grabstein K H
Waldschmidt T J
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.181.4.1399
Published
1995-04-01
Pages
1399-409
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2191957
Subset
IM
Grants
NIAID NIH HHS · AI31265 · United States
External Links
PubMed source DOI: 10.1084/jem.181.4.1399 PMC Full Text View journal details
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