Characterization of the CD4+ T Cell Response to Epstein-Barr Virus during Primary and Persistent Infection

Abstract

The CD8+ T cell response to Epstein-Barr virus (EBV) is well characterized. Much less is known about the evolution of the CD4+ T cell response. Here we show that EBV stimulates a primary burst of effector CD4+ T cells and this is followed by a period of down-regulation. A small population of EBV-specific effector CD4+ T cells survives during the lifelong persistent phase of infection. The EBV-specific effector CD4+ T cells accumulate within a CD27+ CD28+ differentiation compartment during primary infection and remain enriched within this compartment throughout the persistent phase of infection. Analysis of CD4+ T cell responses to individual epitopes from EBV latent and lytic cycle proteins confirms the observation that the majority of the effector cells express both CD27 and CD28, although CD4+ T cells specific for lytic cycle antigens have a greater tendency to express CD45RA than those specific for the latent antigens. In clear contrast, effector CD4+ T cells specific for cytomegalovirus (CMV) accumulate within the CD27− CD28+ and CD27− CD28− compartments. There are striking parallels in terms of the differentiation of CD8+ T cells specific for EBV and CMV. The results challenge current ideas on the definition of memory subsets.

CCR2 Identifies a Stable Population of Human Effector Memory CD4+ T Cells Equipped for Rapid Recall Response

“…2 subset, which is consistent with published data for both CD8 + and CD4 + T cells, showing that anti-EBV cells are less differentiated than anti-CMV cells (9,45,66 (68) or during acute infection with EBV or HIV-1 (69-71). Our finding that, among the agents tested, CMV elicited the greatest responses in the CD127 2 cells, which are relatively abundant in the CCR5 + CCR2 2 subset, is consistent with previous data (58), and suggested that CMV was the virus most often (re)stimulating a systemic immune response.…”

“…CD4 + effector/memory T cells can be divided into subsets based on their patterns of cytokine production (4,6,7) and/or regulatory activities (6,8) and/or surface markers related to T cell activation and survival (9,10). In addition to the changes in these parameters, differentiation from naive to effector/memory T cells is accompanied by significant changes in T cell trafficking within lymphoid compartments (11) and in the cells' acquisition of access to sites in nonlymphoid tissues (12).…”

MHC class II Tetramer Guided Detection of Mycobacterium tuberculosis‐specific CD4+ T Cells in Peripheral Blood from Patients with Pulmonary Tuberculosis

“…EBV). Individual CD4 + T-cell populations directed against EBV latent and lytic cycle proteins express both CD27, CD28 and CD45RA [43], HIV-specific CD4 + T cells are also enriched in the CD27 + CD28 + population [44], suggesting that chronic viral or bacterial infections lead to enrichment of pathogen-specific T cells skewed to an early central memory phenotype. An ex vivo analysis, i.e.…”

Relationship between functional ability in older people, immune system status, and intensity of response to CMV

“…3c). Differentiating CD4+ T cells lose expression of CD27 first and subsequently lose CD28 in a later phase (Amyes et al 2003;van Leeuwen et al 2004). In Fig.…”