The effector to memory transition of CD4 T cells

McKinstry, K. Kai; Strutt, Tara M.; Swain, Susan L.

doi:10.1007/s12026-007-8004-y

Cited by 37 publications

(45 citation statements)

References 72 publications

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“…Malaria infection, which manifests histologically and clinically, involves a very large amount of malaria Ag being in the system. It seems likely that Ag may persist following clearance of viable parasites, as has been suggested for malarial [28] and other pathogens [29,30]. This may maintain the numbers of IFN-gsecreting effector cells as shown for other Ag [24].…”

Section: Discussionmentioning

confidence: 79%

Multiple functions of human T cells generated by experimental malaria challenge

et al. 2009

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Protective immunity generated following malaria infection may be comprised of Ab or T cells against malaria Ag of different stages; however, the short-lived immunity that is observed suggests deficiency in immune memory or regulatory activity. In this study, cellular immune responses were investigated in individuals receiving Plasmodium falciparum sporozoite challenge by the natural (mosquito bite) route as part of a malaria vaccine efficacy trial. Parasitemia, monitored by blood film microscopy and PCR, was subsequently cleared with drugs. All individuals demonstrated stable IFN-c, IL-2 and IL-4 ex vivo ELISPOT effector responses against P. falciparum-infected RBC (iRBC) Ag, 28 and 90 days after challenge. However, infected RBC-specific central memory responses, as measured by IFN-c cultured ELISPOT, were low and unstable over time, despite CD4 1 T cells being highly proliferative by CFSE dilution, and showed an inverse relationship to parasite density. In support of the observation of poor memory, co-culture experiments showed reduced responses to common recall Ag, indicating malaria-specific regulatory activity. This activity could not be accounted for by the expression of IL-10, TGF-b, FOXP3 or CTLA-4, but proliferating T cells expressed high levels of CD95, indicating a pro-apoptotic phenotype. Lastly, there was an inverse relationship between FOXP3 expression, when measured 10 days after challenge, and ex vivo IFN-c measured more than 100 days later. This study shows that malaria infection elicits specific Th1 and Th2 effector cells, but concomitant weak central memory and regulatory activity, which may help to explain the short-lived immunity observed.

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Section: Discussionmentioning

confidence: 79%

Multiple functions of human T cells generated by experimental malaria challenge

et al. 2009

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“…A quantitative gain in antigen-specific T cells represents one important advantage of the memory state but memory CD4 + T cells also differ from naïve T cells by broad functional criteria. Several of these attributes of memory CD4 + T cells allow them to respond much faster and more vigorously than naïve CD4 + T cells upon pathogen challenge 140 . Additionally, subpopulations of memory CD4 + T cells have wider trafficking patterns and some are retained at or near sites of previous infection 141 , which contributes to their ability to be rapidly activated upon local re-infection.…”

Section: Memory Cd4+ T Cell Responses Against Virusesmentioning

confidence: 99%

Expanding roles for CD4+ T cells in immunity to viruses

2012

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Viral pathogens often generate strong CD4+ T cell responses that are best known for their ability to help B cell and CD8+ T cell responses. However, recent studies reveal additional roles for CD4+ T cells, some of which are independent of other lymphocytes, and indicate that memory cells are more effective in most functions than naïve CD4 T cells. Here, we review the full spectrum of antiviral functions of CD4+ T cells, including their helper activities, innate immune induction, and direct anti-viral roles, and suggest how these functions are integrated to provide highly protective responses against viral pathogens.

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“…That the reality is probably more complicated, however, is shown by current information that indicates that there are at least two subsets of memory T cells, both for CD4 and CD8 cells, based upon the anatomical locations of these subsets, their expression of various cell surface markers, and various functional responses based on cytokine secretion and the rapidity of their response (11,21,37). A primary distinction is based upon homing receptors that allow entry into lymphoid tissues.…”

mentioning

confidence: 99%

Phenotypic Definition of Effector and Memory T-Lymphocyte Subsets in Mice Chronically Infected withMycobacterium tuberculosis

Henao-Tamayo

Ordway

Irwin

et al. 2010

Clin Vaccine Immunol

106

108

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The bacterium Mycobacterium tuberculosis remains one of the world's most successful pathogens, a situation that is aggravated by the fact that the existing vaccine, Mycobacterium bovis BCG, is not effective in adults. As with any vaccine, the purpose of giving BCG vaccination is to establish a long-lived state of memory immunity, but whether this is successfully completely established is still unclear. It is generally accepted that memory T cells can be divided into central and effector memory populations by function and by phenotype; however, the majority of data supporting this division have been generated using transgenic mouse models or mice that have recovered from acute viral infections. Tuberculosis, on the other hand, represents a persistent, chronic state of immunity in which the presence of memory T cells is far less well defined. We show here that mice vaccinated with BCG or chronically infected with M. tuberculosis establish antigen-specific populations of cells within the lungs that predominantly express a cellular phenotype consistent with their being effector or effector memory cells. In contrast, cells with a central memory phenotype exist in much lower numbers in the lungs but can be found in significantly larger numbers in the spleen, where they may represent a potential reservoir. These data suggest that the effector-to-central-memory T-cell transition may well be minimal in these persisting mycobacterial infections, and they support a novel hypothesis that this may explain the fundamental basis of the failure of the BCG vaccine in humans.

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The effector to memory transition of CD4 T cells

Cited by 37 publications

References 72 publications

Multiple functions of human T cells generated by experimental malaria challenge

Multiple functions of human T cells generated by experimental malaria challenge

Expanding roles for CD4+ T cells in immunity to viruses

Phenotypic Definition of Effector and Memory T-Lymphocyte Subsets in Mice Chronically Infected withMycobacterium tuberculosis

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