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Blood, 1 August 2008, Vol. 112, No. 3, pp. 680-689. Prepublished online as a Blood First Edition Paper on May 28, 2008; DOI 10.1182/blood-2008-01-132464. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-01-132464v1 112/3/680    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Lin, S.-J. Articles by Welsh, R. M. PubMed PubMed Citation Articles by Lin, S.-J. Articles by Welsh, R. M. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Immune system derived from homeostatic proliferation generates normal CD8 T-cell memory but altered repertoires and diminished heterologous immune responses Sue-Jane Lin1, Alex T. Chen1, and Raymond M. Welsh1 1 Department of Pathology and Program in Immunology and Virology, University of Massachusetts Medical School, Worcester The host responds to lymphopenic environments by acute homeostatic proliferation of T lymphocytes, which acquire phenotypes similar to memory cells. Using T-cell knockout (KO) mice adoptively reconstituted with splenocytes from immunologically naive mice, we examined the immune responses of an immune system derived from homeostatically proliferating (HP) T cells. HP cells mounted relatively normal acute CD8 T-cell responses to lymphocytic choriomeningitis virus (LCMV), but with altered T-cell receptor (TCR) repertoires, and they became functional memory cells capable of recall responses. Although homeostatic proliferation does not normally fully restore T-cell numbers, the CD8+ T-cell pool was completely restored in T-cell KO mice after LCMV infection. CD4 T-cell responses were lower and not fully restored but seemed sufficient to allow for complete differentiation of CD8 memory T cells. The LCMV-immune HP mouse had an immune repertoire heavily biased with LCMV epitope-specific T cells with oligoclonal expansions. LCMV-immune HP mice had reduced cross-reactive and non–cross-reactive CD8 T-cell responses when challenged with a T cell–cross-reactive virus. Thus, whereas an HP immune system is capable of mounting relatively normal acute and memory CD8 T-cell responses, the narrowing of the T-cell repertoire may reduce immune responses to subsequently encountered pathogens. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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