Submitted January 11, 2008
Accepted April 24, 2008
An immune system derived from homeostatic proliferation generates normal CD8 T cell memory but altered repertoires and diminished heterologous immune responses
Sue-Jane Lin, Alex T. Chen, and Raymond M. Welsh*
Department of Pathology, UMASS Medical School, Worcester, MA, United States
* Corresponding author; email: raymond.welsh{at}umassmed.edu.
The host responds to lymphopenic environments by acute homeostatic proliferation of T lymphocytes, which acquire phenotypes similar to memory cells. Using T-cell 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 LCMV, but with altered 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 and 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.
