Immune system derived from homeostatic proliferation generates normal CD8 T-cell memory but altered repertoires and diminished heterologous immune responses.
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.
Department of Pathology and Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Sue-Jane
SJ
Lin
Alex T
AT
Chen
Raymond M
RM
Welsh
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D006706:Homeostasis; D007107:Immune System / Q000166:cytology*; D007109:Immunity; D007156:Immunologic Memory; D051379:Mice; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets