IntroductionThe extraordinary conservation of the subset of T cells expressing V␥V␦-T-cell receptors (TCRs) suggests a nonredundant but still poorly understood role in immune defense. [1][2][3][4][5] The 2 major ␥␦ T-cell subsets in human beings, defined by TCRs containing V␦1 or V␦2 chains, differ in their anatomic localization; V␦1 ϩ T cells predominate within mucosal epithelia and skin whereas V␦2 ϩ T cells are most numerous in peripheral blood. A function in antimicrobial immunity is supported by the dramatic expansion of human ␥␦ T cells in response to a wide range of pathogens and by reduced ␥␦ T-cell numbers and function during disease progression. 4,5 Infectious disease models demonstrated a 2-stage involvement of ␥␦ T cells, the first taking place during the innate phase of primary immune responses and the second being effective during wound repair after pathogen elimination. 4,5 Recently, ␥␦ T cells were postulated to contribute also to memory responses against mycobacteria. 6 Lysates from a large variety of bacteria, parasites, and plants were shown to induce oligoclonal expansion of human V␦2 ϩ T cells in vitro. 3,4 However, ␥␦ T cells differ fundamentally from ␣␤ T cells in the types of antigens (Ags) they recognize. Human ␥␦ T cells recognize small molecular weight nonpeptide Ags, stress-or tumor-induced self Ags, and the CD1 nonpolymorphic lipid Ag-presenting molecules. 3,4,7 The principal pathogen-derived ␥␦ T-cell Ags are isopentenyl pyrophosphate (IPP) and one of its metabolic precursors, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP). [8][9][10] The "simple" mode of Ag recognition (apparent lack of requirement for Ag processing and major histocompatibility complex [MHC] restriction) and the chemical nature of these essential pathogen-specific metabolites suggest a "pattern recognition" type of Ag selectivity by human V␦2 ϩ T cells. 3,4,9 CD1-restricted Ag recognition mainly involves V␦1-TCRs and appears to participate in self-recognition of nonpolymorphic CD1 that may contribute to dendritic cell (DC) maturation 11 (M.B.B. and D. Leslie, personal written communication, July 2002).Responsiveness to microbial metabolic intermediates points to an immediate (as opposed to proliferation/differentiation-dependent) involvement of ␥␦ T cells in antimicrobial processes. Therefore, the migration properties of ␥␦ T cells may resemble those of monocytes and granulocytes that appear early at sites of infection. Chemokines are best known for controlling leukocyte localization during hematopoiesis, initiation of immune responses, and inflammation. 12-14 Traffic patterns and the inflammatory function in leukocytes are largely defined by their chemokine receptor expression and migration profile. Chemokines are divided into 2 major subfamilies, the "homeostatic" and the "inflammatory" chemokines, and their distinctive roles are best exemplified in mature T cells. [14][15][16][17][18] The homeostatic chemokines SLC/CCL21 13 and ELC/CCL19 are constitutively produced in T zones of secondary lymphoid tis...

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