Chronic parasitic infection maintains high frequencies of short-lived ly6c+CD4+ effector T cells that are required for protection against re-infection

dc.creatorPeters, Nathan C.
dc.creatorPagán, Antonio J.
dc.creatorLawyer, Phillip G.
dc.creatorHand, Timothy W.
dc.creatorRoma, Eric Henrique
dc.creatorStamper, Lisa W.
dc.creatorRomano, Audrey
dc.creatorSacks, David L. S.
dc.date2019-09-16T13:57:21Z
dc.date2019-09-16T13:57:21Z
dc.date2014
dc.date.accessioned2023-09-26T21:01:16Z
dc.date.available2023-09-26T21:01:16Z
dc.identifierPETERS, Nathan C. Chronic parasitic infection maintains high frequencies of short-lived Ly6C+CD4+ effector T cells that are required for protection against re-infection. Plos Pathogens, v. 10, n. 12, p. 1-17, Dec. 2014.
dc.identifier1553-7366
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/35604
dc.identifier10.1371/journal.ppat.1004538
dc.identifier1553-7374
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8867846
dc.descriptionEric Henrique Roma. Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta a informação no documento.
dc.descriptionIn contrast to the ability of long-lived CD8+ memory T cells to mediate protection against systemic viral infections, the relationship between CD4+ T cell memory and acquired resistance against infectious pathogens remains poorly defined. This is especially true for T helper 1 (Th1) concomitant immunity, in which protection against reinfection coincides with a persisting primary infection. In these situations, pre-existing effector CD4 T cells generated by ongoing chronic infection, not memory cells, may be essential for protection against reinfection. We present a systematic study of the tissue homing properties, functionality, and life span of subsets of memory and effector CD4 T cells activated in the setting of chronic Leishmania major infection in resistant C57Bl/6 mice. We found that pre-existing, CD44+CD62L2T-bet+Ly6C+ effector (TEFF) cells that are short-lived in the absence of infection and are not derived from memory cells reactivated by secondary challenge, mediate concomitant immunity. Upon adoptive transfer and challenge, non-dividing Ly6C+ TEFF cells preferentially homed to the skin, released IFN-c, and conferred protection as compared to CD44+ CD62L2Ly6C2 effector memory or CD44+CD62L+Ly6C2 central memory cells. During chronic infection, Ly6C+ TEFF cells were maintained at high frequencies via reactivation of TCM and the TEFF themselves. The lack of effective vaccines for many chronic diseases may be because protection against infectious challenge requires the maintenance of pre-existing TEFF cells, and is therefore not amenable to conventional, memory inducing, vaccination strategies.
dc.formatapplication/pdf
dc.languageeng
dc.publisher1553-7374
dc.rightsopen access
dc.subjectChronic infectious diseases
dc.subjectEffector T cells
dc.subjectRe-infection
dc.titleChronic parasitic infection maintains high frequencies of short-lived ly6c+CD4+ effector T cells that are required for protection against re-infection
dc.typeArticle


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