Chronic parasitic infection maintains high frequencies of short-lived Ly6C+CD4+ effector T cells that are required for protection against re-infection.
Chronic parasitic infection maintains high frequencies of short-lived Ly6C+CD4+ effector T cells that are required for protection against re-infection.
复制标题
DOI：
10.1371/journal.ppat.1004538
复制
发表时间：
2014-12
期刊：
影响因子：
6.7
通讯作者：
Sacks DL
中科院分区：
文献类型：
--
作者：
Peters NC;Pagán AJ;Lawyer PG;Hand TW;Henrique Roma E;Stamper LW;Romano A;Sacks DL
In 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+CD62L−T-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-γ, and conferred protection as compared to CD44+CD62L−Ly6C− effector memory or CD44+CD62L+Ly6C− 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. Naturally acquired resistance to reinfection by numerous infectious pathogens including Leishmania, Plasmodium, Mycobacterium, and parasitic worms, typically coincides with an ongoing primary infection. This natural resistance to reinfection, termed concomitant immunity, is often referred to as a memory response and provides the rationale for the vaccine effort against these infectious pathogens. However, immune memory is mediated by populations of long-lived cells that do not require an ongoing primary infection to mediate protection. The requirement for chronic infection to maintain concomitant immunity suggests that the critical cells that mediate this immunity are not memory cells. In the present study we define short-lived effector T cells that pre-exist secondary challenge, not memory cells, as the critical cells that mediate concomitant immunity. These observations provide direct evidence on a cellular level that conventional vaccination strategies against chronic infectious diseases, whose development is predicated upon the belief that concomitant immunity can be mediated by long-lived memory cells, are unlikely to succeed.
登录
查看更多内容
影响因子：
32.4
作者：
Marshall HD;Chandele A;Jung YW;Meng H;Poholek AC;Parish IA;Rutishauser R;Cui W;Kleinstein SH;Craft J;Kaech SM
通讯作者：
Kaech SM
DOI：
10.1084/jem.20021690
发表时间：
2003-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Reinhardt RL;Bullard DC;Weaver CT;Jenkins MK
通讯作者：
Jenkins MK
DOI：
10.4049/jimmunol.1202183
发表时间：
2013-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Nelson RW;McLachlan JB;Kurtz JR;Jenkins MK
通讯作者：
Jenkins MK
白介素（IL）-10在愈合后皮肤中持续的持久性以及抗IL-10受体抗体对无菌治疗的治疗潜力的作用。
DOI：
10.1084/jem.194.10.1497
发表时间：
2001-11-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Belkaid Y;Hoffmann KF;Mendez S;Kamhawi S;Udey MC;Wynn TA;Sacks DL
通讯作者：
Sacks DL
影响因子：
64.8
作者：
Belkaid, Y;Piccirillo, CA;Sacks, DL
通讯作者：
Sacks, DL