CMV exposure drives long-term CD57+ CD4 memory T-cell inflation following allogeneic stem cell transplant

被引：19

作者：

Yeh, Albert C. ^{[1
,2
]}

Varelias, Antiopi ^{[3
,4
]}

Reddy, Anupama ^{[5
]}

Barone, Sierra M. ^{[6
]}

Olver, Stuart D. ^{[3
]}

Chilson, Kate ^{[1
]}

Onstad, Lynn E. ^{[1
]}

Ensbey, Kathleen S. ^{[1
]}

Henden, Andrea S. ^{[3
]}

Samson, Luke ^{[1
,3
]}

Jaeger, Carla A. ^{[1
]}

Bi, Timothy ^{[7
]}

Dahlman, Kimberly B. ^{[8
]}

Kim, Tae Kon ^{[8
]}

Zhang, Ping ^{[1
]}

Degli-Esposti, Mariapia A. ^{[9
]}

Newell, Evan W. ^{[7
]}

Jagasia, Madan H. ^{[8
]}

Irish, Jonathan M. ^{[6
]}

Lee, Stephanie J. ^{[1
,2
]}

Hill, Geoffrey R. ^{[1
,2
]}

机构：

[1] Fred Hutchinson Canc Res Ctr, Clin Res Div, 1100 Fairview Ave N S2-204, Seattle, WA 98109 USA

[2] Univ Washington, Dept Med, Div Med Oncol, Seattle, WA USA

[3] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia

[4] Univ Queensland, Facuty Med, Brisbane, Qld, Australia

[5] Prism Bioanalyt, Durham, NC USA

[6] Vanderbilt Univ, Dept Cell & Dev Biol, 221 Kirkland Hall, Nashville, TN 37235 USA

[7] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA

[8] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN USA

[9] Monash Univ, Dept Microbiol, Biomed Discovery Inst, Infect & Immun Program, Clayton, Vic 3168, Australia

来源：

BLOOD | 2021年 / 138卷 / 26期

基金：

美国国家卫生研究院;

关键词：

CYTOMEGALOVIRUS REPLICATION; II TETRAMERS; SEROSTATUS; RECONSTITUTION; LYMPHOCYTES; EXPRESSION; RECIPIENTS; INFECTION; EPITOPES; DISEASE;

D O I：

10.1182/blood.2020009492

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Donor and recipient cytomegalovirus (CMV) serostatus correlate with transplant-related mortality that is associated with reduced survival following allogeneic stem cell transplant (SCT). Prior epidemiologic studies have suggested that CMV seronegative recipients (R-) receiving a CMV-seropositive graft (D+) experience inferior outcomes compared with other serostatus combinations, an observation that appears independent of viral reactivation. We therefore investigated the hypothesis that prior donor CMV exposure irreversibly modifies immunologic function after SCT. We identified a CD4(+)/CD57(+)/CD27(-) T-cell subset that was differentially expressed between D+ and D- transplants and validated results with 120 patient samples. This T-cell subset represents an average of 2.9% (D-/R-), 18% (D-/R+), 12% (D+/R-), and 19.6% (D+/R+) (P < .0001) of the total CD4(+) T-cell compartment and stably persists for at least several years post-SCT. Even in the absence of CMV reactivation postSCT, D+/R- transplants displayed a significant enrichment of these cells compared with D-/R- transplants (P = .0078). These are effector memory cells (CCR7-/CD45RA(+/-)) that express T-bet, Eomesodermin, granzyme B, secrete Th1 cytokines, and are enriched in CMV-specific T cells. These cells are associated with decreased T-cell receptor diversity (P < .0001) and reduced proportions of major histocompatibility class (MHC) II expressing classical monocytes (P < .0001), myeloid (P = .024), and plasmacytoid dendritic cells (P = .0014). These data describe a highly expanded CD4(+) T-cell population and putative mechanisms by which prior donor or recipient CMV exposure may create a lasting immunologic imprint following SCT, providing a rationale for using D- grafts for R- transplant recipients.

引用

页码：2874 / 2885

页数：12