IL-4 has a critical, mouse strain-limited role in innate memory CD8+ T cell development. (115.19)

Abstract

Abstract Mice have large numbers of innate memory cells: CD8+ T cells that develop functional and phenotypic memory cell characteristics in the absence of purposeful immunization. The role of IL-4 production by iNKT cells in innate memory cell development is shown by an ~80% decrease in splenic memory phenotype CD8+ T cell number in IL-4-, IL-4Rα-, Stat6- and CD1d KO BALB/c mice and an ~1/3 normal basal IL-4 level in CD1d KOs. The stimulatory effect of IL-4 on innate memory cell development is first observed in CD8hiCD4lo thymocytes and persists through adulthood. Anti-IL-4 mAb decreases innate memory cell number in thymus and spleen in immature mice, but only in thymus in adults. In contrast to BALB/c mice, IL-4Rα deficiency has little effect on CD8+ memory phenotype T cell number in C57BL/6 mice. This BALB/c - C57BL/6 difference is not associated with appreciable differences in basal total body or thymic IL-4 expression, CD8+ T cell IL-4Rα expression or IL-4 responsiveness, but is associated with greater IL-15Rα and IL-2/15Rβ expression and IL-15 responsiveness by C57BL/6 than BALB/c CD8+ splenocytes. In 5 additional mouse strains studied, 3 resemble BALB/c and 2 resemble C57BL/6 mice with regard to the IL-4 stimulation of innate memory cell development; an IL-4 effect correlates positively with thymic memory phenotype CD8+ T cell number. Thus, IL-4 produced by thymic NKT cells has a major role in memory phenotype CD8+ T cell development that varies among mouse strains.