According to researchers costimulation modulation will be able to uncouple protective responses from immunopathological responses of memory T cells to influenza virus.
The researchers reported that previous studies showed immunotherapies targeting CD28 costimulation may affect memory T cell responses. However, the impact of CD28 inhibition on physiological secondary responses and protective immunity by memory T cells has not been elucidated.
Dr. John R. Teijaro from University of Maryland School of Medicine, Baltimore, and team studied the impact of inhibiting CD28 costimulation (using the approved immunomodulator CTLA4Ig) on memory T cell-driven secondary responses to influenza challenge.
The results showed that CTLA4Ig-treated mice had better clinical outcomes to influenza challenge than did control mice, but CTLA4Ig treatment did not impair the ability of hemagglutinin-specific memory T cells to clear virus.
The researchers noted a contrast in the findings with the suppressive effects of CTLA4Ig on the primary responses of memory T cells to influenza.
CTLA4Ig inhibited spleen or lymphoid-derived nave and memory CD4 T cells while leaving in situ lung memory CD4 T cell responses intact.
The report indicates that CTLA4Ig differentially affected lymphoid and nonlymphoid responses to influenza challenge, inhibiting proliferation and egress of lymphoid nave and memory T cells, while leaving lung-resident memory CD4 T cell responses intact.
Further it was seen that lung memory CD4 T cells retained their effector function in the presence of CTLA4Ig, suggesting that effector function from lung memory CD4 T cells is intrinsically independent of CD28 costimulation.
Our results reveal a novel role for CD28-based immunotherapy for optimizing antiviral secondary responses by differential effects on lymphoid versus lung memory CD4 T cells, the authors conclude