Antigen persistence regulates the functional characteristics and stability of secondary Th1 responders (163.10)

Abstract

Abstract CD4+ memory T cells exhibit a skewing towards high functional avidity during memory maintenance. We find that heterologous rechallenge of LCMV-induced CD4+ memory T cells from LCMV-immune mice with a recombinant Listeria monocytogenes that secretes the LCMV-derived glycoprotein peptide GP61-80 (Lm-gp61) preserves the high functional avidity of secondary Th1 effector cells and their subsequent stability within the memory pool. Conversely, adoptive transfer of CD4+ memory T cells into naïve mice prior to rechallenge results in a loss of functional avidity by secondary Th1 effector cells and poor maintenance of secondary memory. Loss of function is not due to the transfer itself, as transfer into LCMV-immune hosts allows secondary Th1 effector cells to maintain their enhanced function after Lm-gp61 challenge. LCMV-immune mice clear an Lm-gp61 infection more quickly than naïve mice, suggesting that the infectious environment of the secondary challenge is critical for the acquisition of secondary Th1 effector function. Artificially extending the inflammatory response alone following secondary challenge does not adversely affect the functional avidity of CD4+ memory T cells into LCMV-immune recipients. Instead, our findings indicate that upon rechallenge, secondary Th1 effector and memory cells are exquisitely susceptible to functional fine-tuning based on the persistence of infectious antigen.