Adaptive immune response of Vgamma2Vdelta2 T cells: a new paradigm

Abstract

The role of gammadelta T cells in adaptive immunity remains uncertain. Recent studies have demonstrated that a unique subset of gammadelta T cells in primates can mount adaptive immune responses during mycobacterial infections. This Review discusses notable similarities and differences in adaptive immune responses between non-peptide-specific gammadelta T cells and peptide-specific alphabeta T cells, and discusses both the molecular basis for gammadelta T-cell responses and potential functions of these enigmatic cells.

Fig. 1

Systemic Mycobacterium bovis Calmette–Guérin (BCG) infection introduced by intravenous inoculation can result in a preferential increase in Vγ2Vδ2⁺ T cells in bronchial alveolar lavage (BAL) fluid. Note the lack of increase in numbers of CD4⁺ and CD8⁺ T cells at the time the increase in Vγ2Vδ2⁺ T cells is identified. Shown are mean values with the error bars of standard error of the mean (SEM) from four animals.

Fig. 2

Proposed migration of Vγ2Vδ2 T cells to lungs or other epithelial compartments during infections. MIP-1α, MIP-1β and RANTES (ligands for CCR5) produced after infections in the pulmonary compartment might have a role in chemoattracting CCR5⁺ Vγ2Vδ2 T cells to the lung from the circulation or lymphoid tissues [–43]. Because Vγ2Vδ2 T cells also express CXCR3, these cells are probably attracted by chemokines, such as MIG, IP-10 and I-TAC. The chemoattracting process and IL-12 might also involve the NKPR1a-mediated endothelia migration pathway [–45]. It is also probable that chemokines produced in the blood by activated Vγ2Vδ2 T cells themselves or other immune cells initiate the transendothelial migration of these γδ T cells to the lung from the circulation during systemic infection or immune activation. Abbreviations: IL-12, interleukin-12; IP-10, interferon (IFN)-inducible protein 10; I-TAC, IFN-inducible T-cell α-chemoattractant; MIG, monokine induced by IFN-γ; MIP-1α, macrophage inflammatory protein-1α; NKRP1a, NK receptor protein 1a (CD161).