AUTHOR=Nateghi-Rostami Mahmoud , Sohrabi Yahya 

TITLE=Memory T cells: promising biomarkers for evaluating protection and vaccine efficacy against leishmaniasis

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1304696

DOI=10.3389/fimmu.2024.1304696

ISSN=1664-3224

ABSTRACT=<p>Understanding the immune response to <italic>Leishmania</italic> infection and identifying biomarkers that correlate with protection are crucial for developing effective vaccines. One intriguing aspect of <italic>Leishmania</italic> infection is the persistence of parasites, even after apparent lesion healing. Various host cells, including dendritic cells, fibroblasts, and Langerhans cells, may serve as safe sites for latent infection. Memory T cells, especially tissue-resident memory T cells (T<sub>RM</sub>), play a crucial role in concomitant immunity against cutaneous <italic>Leishmania</italic> infections. These T<sub>RM</sub> cells are long-lasting and can protect against reinfection in the absence of persistent parasites. CD4<sup>+</sup> T<sub>RM</sub> cells, in particular, have been implicated in protection against <italic>Leishmania</italic> infections. These cells are characterized by their ability to reside in the skin and rapidly respond to secondary infections by producing cytokines such as IFN-γ, which activates macrophages to kill parasites. The induction of CD4<sup>+</sup> T<sub>RM</sub> cells has shown promise in experimental immunization, leading to protection against <italic>Leishmania</italic> challenge infections. Identifying biomarkers of protection is a critical step in vaccine development and CD4<sup>+</sup> T<sub>RM</sub> cells hold potential as biomarkers, as their presence and functions may correlate with protection. While recent studies have shown that <italic>Leishmania</italic>-specific memory CD4<sup>+</sup> T-cell subsets are present in individuals with a history of cutaneous leishmaniasis, further studies are needed to characterize CD4<sup>+</sup> T<sub>RM</sub> cell populations. Overall, this review highlights the importance of memory T cells, particularly skin-resident CD4<sup>+</sup> T<sub>RM</sub> cells, as promising targets for developing effective vaccines against leishmaniasis and as biomarkers of immune protection to assess the efficacy of candidate vaccines against human leishmaniasis.</p>