Differing Roles of Inflammation and Antigen in T Cell Proliferation and Memory Generation

Abstract

Recent studies have demonstrated that viral and bacterial infections can induce dramatic in vivo expansion of Ag-specific T lymphocytes. Although presentation of Ag is critical for activation of naive T cells, it is less clear how dependent subsequent in vivo T cell proliferation and memory generation are upon Ag. We investigated T cell expansion and memory generation in mice infected alternately with strains of Listeria monocytogenes that contained or lacked an immunodominant, MHC class I-restricted T cell epitope. We found substantial differences in the responses of effector and memory T cells to inflammatory stimuli. Although effector T cells undergo in vivo expansion in response to bacterial infection in the absence of Ag, memory T cells show no evidence for such bystander activation. However, Ag-independent expansion of effector T cells does not result in increased memory T cell frequencies, indicating that Ag presentation is critical for effective memory T cell generation. Early reinfection of mice with L. monocytogenes before the maximal primary T cell response induces typical memory expansion, suggesting that the capacity for a memory T cell response exists within the primary effector population. Our findings demonstrate that T cell effector proliferation and memory generation are temporally overlapping processes with differing requirements for Ag.

Cutting Edge: Antigen-Independent CD8 T Cell Proliferation

“…Inflammatory cytokine and chemokine secretion has been demonstrated in L. monocytogenes-infected tissues and the local cytokine milieu likely provides the exogenous stimuli that promote continued T cell division for 7-8 days following initial infection. In support of this, we have recently shown that increased expansion of activated T cells can be achieved by inflammation induced by a second bacterial infection in the absence of specific Ag (27). Whether IL-7 or IL-15 plays a role in promoting in vivo proliferation of L. monocytogenes-specific T lymphocytes during infection remains unknown and is currently being investigated.…”

Bystander Activation of CD8+ T Cells Contributes to the Rapid Production of IFN-γ in Response to Bacterial Pathogens

“…Our findings that CD8 ϩ T cells (as well as NK cells) are induced to express IFN-␥ within 16 h after challenge with viable L. monocytogenes in vivo support this concept. Together, these data suggest that bystander cytokine activation of CD8 ϩ T cells may operate at several levels in contributing to host immunity: first, by providing an additional source of IFN-␥ during the early phase of response to infection; second, in expansion of effector T cells (46); and third, by nonspecifically maintaining the memory T cell pool (47). These results imply that prior antigenic experience provides the host not only with specific memory T cells, but a pool of cells, which collectively can contribute to innate immunity against subsequent unrelated infection.…”

Quantitation of CD8+ T Cell Expansion, Memory, and Protective Immunity After Immunization with Peptide-Coated Dendritic Cells

“…This may be due to bacterial products and/or proinflammatory cytokines that promote the maturation of DCs to a highly stimulatory state for naive T cells or to the production of growth-promoting cytokines that drive CD8 ϩ T cell proliferation upon activation (20,25). We asked whether LM infection would alter the magnitude or kinetics of the CD8 ϩ T cell response to peptide-coated mature BMDCs.…”

“…ϩ T cell expansion kinetics can be affected by the inflammatory response to infection (25). This may be due to bacterial products and/or proinflammatory cytokines that promote the maturation of DCs to a highly stimulatory state for naive T cells or to the production of growth-promoting cytokines that drive CD8 ϩ T cell proliferation upon activation (20,25).…”