Publication Date


Document Type

Doctoral Dissertation

Academic Program

Immunology and Microbiology


Department of Pathology

First Thesis Advisor

Susan Swain


Influenza Infection, CD4 T cells, Antigen, Cytotoxic CD4 T cells, CD4 differentiation


CD4 T cells differentiate into multiple effector subsets that mediate pathogen clearance. ThCTL are anti-viral effectors with MHC-II restricted cytotoxicity. The factors regulating ThCTL generation are unclear, in part due to a lack of a signature marker. I show here that in mice, NKG2C/E identifies ThCTL that develop in the lung during influenza A virus (IAV) infection. ThCTL phenotype indicates they are highly activated effectors with high levels of binding to P-selectin, T-bet, IFNγ production, and degranulation. ThCTL express increased levels of granzymes and perforin and lower levels of genes associated with memory and recirculation compared to non-ThCTL lung effectors. ThCTL are also restricted to the site of infection, the lung in IAV and systemically in LCMV. ThCTL require Blimp-1 for their differentiation, suggesting a unique effector CD4 population. As ThCTL are highly activated, they also require antigen signaling post priming during IAV infection. Late antigen was necessary and sufficient for the differentiation of ThCTL. In the context of late antigen encounter, ThCTL surprisingly do not require CD80 and CD86 costimulation for their differentiation. Additionally ThCTL do not require late IL-2 for their differentiation and instead require late IL-15 signals for their efficient generation. Thus these data suggest ThCTL are marked by the expression of NKG2C/E and represent a unique CD4 effector population specialized for cytotoxicity.



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