Accumulation of γδ T Cells in the Lungs and Their Regulatory Roles in Th1 Response and Host Defense against Pulmonary Infection with Cryptococcus neoformans

Abstract

The present study was designed to elucidate the role of γδ T cells in the host defense against pulmonary infection with Cryptococcus neoformans. The γδ T cells in lungs commenced to increase on day 1, reached a peak level on day 3 or 6, and then decreased on day 10 after intratracheal infection. The increase of these cells was similar in monocyte chemoattractant protein (MCP)-1-deficient mice, although that of NK and NKT cells was significantly reduced. The number of live microorganisms in lungs on days 14 and 21 was significantly reduced in mice depleted of γδ T cells by a specific mAb compared with mice treated with control IgG. Similarly, elimination of this fungal pathogen was promoted in γδ T cell-deficient (TCR-δ−/−) mice compared with control littermate mice. Finally, lung and serum levels of IFN-γ on days 7 and 14 and on day 7 postinfection, respectively, were significantly higher in TCR-δ−/− mice than in littermate mice, whereas levels of TGF-β showed the opposite results. IL-4 and IL-10 were not different between these mice. IFN-γ production by draining lymph node cells upon restimulation with cryptococcal Ags was significantly higher in the infected TCR-δ−/− mice than in control mice. Our results demonstrated that γδ T cells accumulated in the lungs in a manner different from NK and NKT cells after cryptococcal infection and played a down-modulatory role in the development of Th1 response and host resistance against this fungal pathogen.

Oncogene MYCN regulates localization of NKT cells to the site of disease in neuroblastoma

“…Selective genetic deletion of NKT cells in Jα18 -/-mice suppressed Th1 responses and prevented clearance of the infection. Ccl2 production preceded NKT cell-mediated inflammatory responses in wild-type mice, whereas the lack of lung infiltration with NKT cells in Ccl2 -/-mice, although NKT cells remained functional, was associated with a failure to develop protective immunity against the fungus (46). our data strongly suggest that by repressing CCL2, a key chemokine responsible for NKT cell chemoattraction, MYCN may effectively prevent NKT cell function in neuroblastoma.…”

Deficiency of γδ T lymphocytes contributes to mortality and immunosuppression in sepsis

“…Increased numbers of ␥␦ T cells have been shown to be associated with a variety of infectious conditions (9). Studies have indicated that an accumulation of ␥␦ T cells was found in the lungs of mice with sepsis (23) and pulmonary bacterial infection (44). Nonetheless, ␥␦ T cells seem to have a complex role in host defense because the depletion of these cells has been shown to lead to not only changes in Th1 and Th2-type responses but also can be either detrimental or protective to host survival/ infection depending on the specific pathogen nature and stage of infection (28).…”

The Plasticity of γδ T Cells: Innate Immunity, Antigen Presentation and New Immunotherapy

“…For instance, the normal mouse lung contains 10 5 γδ T cells, and after intratracheal infection with Cryptococcus neoformans, γδ T cell number increases in 3-6 days. The depletion of pulmonary γδ T cells in the lung decreases the time of clearance, suggesting that γδ T cells down-modulating the Th1 inflammatory response may play a regulatory role during the infection (18). In humans, several studies have reported in vitro reactivity of both human Vδ2 and Vδ1 against normal cells infected with viruses, parasites and bacteria as well as tumor cells (19).…”