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Learning to remember: generation and maintenance of T-cell memory.

Immunologic memory results from a carefully coordinated interplay between cells of the immune system. In this review, we explore various aspects of the nature, generation, and maintenance of T lymphocyte-mediated immunologic memory. In light of the demonstrated heterogeneity of the memory T-cell pool, we hypothesize that subsets of memory T cells instructed to mature to distinct differentiation stages may differ, not only in functional and homing properties, but also in the conditions they require for survival, including antigen persistence and cytokine environment. Hence, according to this hypothesis, distinct memory T-cell subsets result from the nature and timing of the signals provided by the immune environment and occupy distinct niches. Intracellular and extracellular molecular mechanisms that underlie and modulate T-cell memory are discussed.

Animals↗

How does cross-reactive stimulation affect the longevity of CD8+ T cell memory?

Immunological memory--the ability to "remember" previously encountered pathogens and respond faster upon re-exposure is a central feature of the immune response in vertebrates. The cross-reactive stimulation hypothesis for the maintenance of memory proposes that memory cells specific for a given pathogen are maintained by cross-reactive stimulation following infections with other (unrelated) pathogens. We use mathematical models to examine the cross-reactive stimulation hypothesis. We find that: (i) the direct boosting of cross-reactive lineages only provides a very small increase in the average longevity of immunological memory; (ii) the expansion of cross-reactive lineages can indirectly increase the longevity of memory by reducing the magnitude of expansion of new naive lineages which occupy space in the memory compartment and are responsible for the decline in memory; (iii) cross-reactive stimulation results in variation in the rates of decline of different lineages of memory cells and enrichment of memory cell population for cells that are cross-reactive for the pathogens to which the individual has been exposed.

Animals↗

Immunological memory.

Most of the antigen-specific T and B cells participating in the primary immune response are rapidly eliminated, but some of the cells survive and become long-lived memory cells. There have been a number of recent developments on the features and functions of memory cells.

B-Lymphocytes↗

Immunologic memory in the placenta: a lymphocyte recirculation hypothesis.

The placenta is an immunologically unique organ where a balance between maternal immunity and fetoplacental well-being must be maintained for successful pregnancy to occur. The intervillous blood is important in this context, yet little is known about local immunologic processes, particularly how placenta-specific memory immune responses are maintained. Using malaria as an illustrative case, we describe an hypothetical model in which recirculation of memory T lymphocytes from the intervillous blood to local lymphoid tissue facilitates maintenance of local memory immunity. This explains how memory cells might be retained when the placenta is expelled at parturition and thus remain available for rapid recall from the local lymphoid tissue to the intervillous space when exposure to the same antigenic stimulus occurs in subsequent pregnancies. Study of cell-mediated immunity to infections like malaria in the intervillous blood and the use of animal models will be necessary to provide proof for this hypothesis.

Female↗

Lymphocyte transformation induced by autologous cells. V. Generation of immunologic memory and specificity during the autologous mixed lymphocyte reaction.

Lymphocyte proliferation in vitro may follow antigen recognition and serve as a correlate of cell-mediated immunity. Lymphocyte proliferation can also be simulated by nonimmune mechanisms as, for example, following culture with plant lectin, lipopolysaccharides, or staphylococcal protein A (1). The autologous mixed lymphocyte reaction (MLR) refers to the proliferation of T lymphocytes cultured with autologous mon-T lymphocytes (2,3). The purpose of this study was to determine whether lymphocyte proliferation in the autologous MLR results from immune or nonimmune mechanisms. We have shown that the autologous MLR has two classical attributes of an immune phenomenon: memory and specificity.

Antibody Specificity↗

Immunological memory in mice to adult Hymenolepis diminuta (Cestoda).

Following a primary infection with Hymenolepsis diminuta mice were found to be strongly resistant to a challenge infection over a period of eight months. Challenge was by three cysticercoids administered orally, or by inserting into the duodenum one 7-day-old strobilate worm recovered from a donor mouse. Autopsy of immunized mice 6, 8, and 9 days after challenge showed that challenge worms established but that, with few exceptions, only shunted or destrobilated worms remained. Autopsy of recently immunized mice, at daily intervals following challenge, confirmed that transplanted worms establish as well in immunized as in naive mice, and showed that worms grow normally for the first 48 hr but between 48 to 120 hr most worms destrobilate or are lost. In naive mice, transplanted worms survive and grow, approximately doubling their weight daily for at least 6 days (144 hr). The results provide insight to the problem of developing a useful vaccine and the location of memory cells.

Animals↗