Alterations in Ag-specific naïve CD4 T cell precursors after sepsis impairs their responsiveness to pathogen challenge1

• Published in: The Journal of immunology (1950) 2015-01, Vol.194 (4), p.1609-1620
• Main Authors: Cabrera-Perez, Javier, Condotta, Stephanie A., James, Britnie R., Kashem, Sakeen W., Brincks, Erik L., Rai, Deepa, Kucaba, Tamara A., Badovinac, Vladimir P., Griffith, Thomas S.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1401711

Patients surviving the acute stages of sepsis develop compromised T cell immunity and increased susceptibility to infection. Little is known about the decreased CD4 T cell function after sepsis. We tracked the loss and recovery of endogenous Ag-specific CD4 T cell populations after cecal-ligation and puncture (CLP)-induced sepsis, and analyzed the CD4 T cell response to heterologous infection during or after recovery. We observed that the sepsis-induced early loss of CD4 T cells was followed by thymic-independent numerical recovery in the total CD4 T cell compartment. Despite this numerical recovery, we detected alterations in the composition of naïve CD4 T cell precursor pools, with sustained quantitative reductions in some populations. Mice that had experienced sepsis and were then challenged with epitope-bearing, heterologous pathogens demonstrated significantly reduced priming of recovery-impaired Ag-specific CD4 T cell responses, both in magnitude of expansion and functional capacity on a per-cell basis, which also correlated with intrinsic changes in Vβ clonotype heterogeneity. Our results demonstrate the recovery of CD4 T cells from sepsis-induced lymphopenia is accompanied by alterations to the composition and function of the Ag-specific CD4 T cell repertoire.