Editors' ChoiceIMMUNITY

With Age Comes Improved Memory

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Science Translational Medicine  20 Feb 2013:
Vol. 5, Issue 173, pp. 173ec34
DOI: 10.1126/scitranslmed.3005925

Aging is often blamed for forgetfulness or lapses in memory; however, this cannot be said for our immune system. One of the foundations of adaptive immunity is the ability to develop specific memory against an encountered pathogen. Immune memory allows a rapid defense to be mounted after subsequent infection or exposure. Now, new evidence reveals that specific memory lymphocytes can develop as we age, in the absence of any encounter with a specific pathogen.

Su et al. were investigating human CD4+ T lymphocyte specificities when they made an unusual observation: Many humans who had never been exposed or infected with viruses such as CMV, HSV, or HIV carried T cells specific for these viruses. Amazingly, these specific-viral CD4 lymphocytes were phenotypically characterized as immune memory cells by the expression of CD45RO. A key feature of true memory cells is the ability to rapidly produce cytokines; therefore, the researchers isolated HIV-specific CD4+ T cells from healthy nonexposed adult humans and stimulated them. Supporting their observations, the HIV-specific T cells with CD45RO rapidly made interferon, whereas CD45RO-negative—naïve—cells made significantly less interferon. Additionally, gene expression analysis of the HIV-specific T cells revealed gene signatures that were consistent with immune memory cells. The authors wondered whether exposure to environmental stimuli could lead to cross-reactive memory lymphocytes, explaining how humans could develop memory against HIV without being infected. Indeed, peptides from common soil and gut microbiota elicited cross-reactive HIV-specific CD4+ T cells. In contrast to adults, memory phenotype CD4+ T cells were not found in neonate umbilical cord blood, confirming the authors’ hypothesis that memory develops overtime as humans age, even in the absence of specific exposure.

This work challenges the current immune system paradigm of memory development in humans. It highlights that exposure to benign environmental organisms can generate pathogen-specific memory and that specific vaccinations may provide broad immune protection from other pathogens through T cell cross-reactivity. These findings offer new critical insights into the human immune system and have direct implications for future vaccine development.

L. F. Su et al., Virus-specific CD4+ memory-phenotype T cells are abundant in unexposed adults. Immunity 38, 1–11 (2013). [Abstract]

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