CD8+ T cell contraction is controlled by early inflammation

Abstract

Pathogen-specific CD8(+) T cells expand in number after infection and then their numbers invariably contract by 90-95%, leaving a stable memory cell pool. The chief features of this response are programmed early after infection; however, the factors regulating contraction are mostly undefined. Here we show that antibiotic treatment before Listeria monocytogenes infection induced numbers of protective memory CD8(+) T cells similar to those in control infected mice, by a pathway without contraction. The absence of contraction correlated with decreased early inflammation and interferon-gamma production and an increased fraction of CD8(+) T cells expressing the interleukin 7 receptor at the peak of the response. Thus, contraction is controlled by early inflammation but is not essential for the generation of protective memory CD8(+) T cells after infection.

IFN-γ Receptor Signaling Regulates Memory CD8+ T Cell Differentiation

“…On the one hand, it promotes CD8 + T cell expansion and memory formation (25,26). On the other hand, it induces contraction of the effector CD8 + T cell pool (23,27), partially via its proapoptotic effects (18)(19)(20). Hence, agonistic and antagonistic effects of IFN-g must be balanced to generate functional CD8 + T cell responses during the course of infection.…”

“…IFN-g-responsive CD11b + cells counterregulate CD62L downregulation and expansion of OT-I cells during priming but are not sufficient to prevent the accumulation of T EMs in IFNgR 2/2 mice IFN-g regulates the magnitude of CD8 + T cell responses prior to the contraction phase (23), partially via its action on suppressive CD11b + cells (17). In this early phase of the response, the frequency of CD62L lo CD8 + effector T cells indicates the relative abundance of T EMs in the ensuing memory pool (22).…”

The role of apoptosis in the development and function of T lymphocytes

“…As a result, the peak immune response is also diminished. However, a significant population of memory cells is still generated without a contraction phase [204]. Whether early inflammation controls CD8 + T cell contraction phase through IFNγ is still an open question and needs further investigation.…”

Persistent Antigen Presentation after Acute Vesicular Stomatitis Virus Infection

“…This phase appears to be antigen independent and is programmed during the initiation of the response (2). The level of inflammation early during priming is also a key determinant of the overall expansion and contraction of the response, with inflammatory mediators exerting both positive and negative effects on the response depending on the context in which they are perceived (3,8,9,25,49). The surviving cells eventually form the memory population that is maintained at a relatively constant level by homeostatic turnover.…”