Self-recognition of CD1 by γ/δ T cells:: Implications for innate immunity

被引:317
作者
Spada, FM
Grant, EP
Peters, PJ
Sugita, M
Melián, A
Leslie, DS
Lee, HK
van Donselaar, E
Hanson, DA
Krensky, AM
Majdic, O
Porcelli, SA
Morita, CT
Brenner, MB
机构
[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA
[2] Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands
[3] Univ Iowa, Dept Internal Med, Div Rheumatol, Iowa City, IA 52242 USA
[4] Univ Iowa, Interdisciplinary Grad Program Immunol, Iowa City, IA 52242 USA
[5] Virginia Mason Res Ctr, Seattle, WA 98101 USA
[6] Stanford Univ, Dept Pediat, Div Immunol & Transplantat Biol, Stanford, CA 94305 USA
[7] Univ Vienna, Inst Immunol, A-1090 Vienna, Austria
关键词
T lymphocytes; T cell antigen receptors gamma/delta; CD1; cytolysis; granulysin;
D O I
10.1084/jem.191.6.937
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The specificity of immunoglobulins and alpha/beta T cell receptors (TCRs) provides a framework for the molecular basis of antigen recognition. Yet, evolution has preserved a separate lineage of gamma/delta antigen receptors that share characteristics of both immunoglobulins and alpha/beta TCRs but whose antigens remain poorly understood. We now show that T cells of the major tissue gamma/delta T cell subset recognize nonpolymorphic CD1c molecules. These T cells proliferated in response to CD1(+) presenter cells, lysed CD1c(+) targets, and released T helper type 1 (Th1) cytokines. The CD1c-reactive gamma/delta T cells were cytotoxic and used both perforin- and Fas-mediated cytotoxicity. Moreover, they produced granulysin, an important antimicrobial protein. Recognition of CD1c was TCR mediated, as recognition was transferred by transfection of the gamma/delta TCR. Importantly, all CD1c-reactive gamma/delta T cells express V delta 1 TCRs, the TCR expressed by most tissue gamma/delta T cells. Recognition by this tissue pool of gamma/delta T cells provides the human immune system with the capacity to respond rapidly to nonpolymorphic molecules on professional antigen presenting cells (APCs) in the absence of foreign antigens that may activate or eliminate the APCs. The presence of bactericidal granulysin suggests these cells may directly mediate host defense even before foreign antigen-specific T cells have differentiated.
引用
收藏
页码:937 / 948
页数:12
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