Immune system derived from homeostatic proliferation generates normal CD8 T-cell memory but altered repertoires and diminished heterologous immune responses

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Department of Pathology; Program in Immunology and Virology

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Adoptive Transfer; Animals; CD8-Positive T-Lymphocytes; *Cell Proliferation; *Homeostasis; Immune System; Immunity; *Immunologic Memory; Mice; Mice, Knockout; T-Lymphocyte Subsets


Life Sciences | Medicine and Health Sciences


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.

DOI of Published Version



Blood. 2008 Aug 1;112(3):680-9. Epub 2008 May 28. Link to article on publisher's site

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