Roles of NKT cells in resistance against infection with Toxoplasma gondii and in expression of heat shock protein 65 in the host macrophages

The possible contribution of NKT cells to resistance to Mycobacterium tuberculosis infection remains unclear. In this paper we characterized the Vα14 NKT cell population following infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG). BCG infection determined an early expansion of Vα14 NKT cells in liver, lungs, and spleen, which peaked on day 8 and was sustained until day 30. However, an NK1.1+ Vα14 NKT population preferentially producing IFN-γ predominated at an early stage (day 8), which was substituted by an NK1.1− population preferentially producing IL-4 at later stages (day 30). Despite the fact that Vα14 NKT cell-deficient mice eliminated BCG as did control mice, they had significantly higher numbers of granulomas in liver and lungs. Additionally, while control mice developed organized small granulomas, those in Vα14 NKT-deficient mice had signs of caseation, large cellular infiltrates, and some multinucleated macrophages, suggesting that Vα14 NKT cells may actually work as anti-inflammatory cells by limiting excessive lymphocyte influx and tissue pathology. In agreement, we found an increased spontaneous production and mRNA expression of TNF-α in liver and lungs of Vα14 NKT-deficient mice, whose neutralization in vivo by anti-TNF-α mAbs consistently reduced the number of granulomas in liver and lungs. Together, our results support a regulatory role for Vα14 NKT cells in the course of BCG infection through their ability to limit the extent of inflammatory response and point to an important role for this cell subset as a regulator of the balance between protective responses and immunopathology.

Section: Discussionmentioning

confidence: 83%

An Anti-Inflammatory Role for Vα14 NK T cells inMycobacterium bovisBacillus Calmette-Guérin-Infected Mice

Dieli

Taniguchi

Kronenberg

et al. 2003

“…Interestingly, Nakano and coworkers (49,50) reported the inverse relationship in the roles of these cells in host defense against Toxoplasma gondii infection. Depletion of ␥␦ T cells led to reduced production of IFN-␥ and aggravation of this infection, whereas the opposite results were observed in mice lacking NKT cells.…”

Section: Discussionmentioning

confidence: 99%

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

Uezu

Kawakami

Miyagi

et al. 2004

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.

“…Therefore, it appears that NKT cells would not play a major role, if any, in the protective activity of the V␤8 ϩ T cell population in the brain of infected mice. In relation to this, Nakano et al (26) recently reported the possibility that NKT cells play a suppressive role on IFN-␥-mediated, protective immunity against acute acquired infection with T. gondii in BALB/c mice.…”

Section: Discussionmentioning

confidence: 99%

TCR Vβ8+ T Cells Prevent Development of Toxoplasmic Encephalitis in BALB/c Mice Genetically Resistant to the Disease

Kang

Liesenfeld

Remington

et al. 2003

BALB/c are genetically resistant to development of toxoplasmic encephalitis (TE) when infected with Toxoplasma gondii, whereas CBA/Ca mice are susceptible. We compared TCR Vβ chain usage in lymphocytes infiltrated into brains between these animals following infection. TCR Vβ8+ cells were the most frequent T cell population in brains of infected, resistant BALB/c mice, whereas TCR Vβ6+ T cells were more prevalent than Vβ8+ T cells in brains of infected, susceptible CBA/Ca mice. Adoptive transfer of Vβ8+ immune T cells, obtained from infected BALB/c mice, prevented development of TE and mortality in infected athymic nude mice that lack T cells. In contrast, adoptive transfer of Vβ6+ immune T cells did not prevent development of TE or mortality in the nude mice. The protective activity of Vβ8+ immune T cells was greater than that of the total Vβ8− population. In addition, Vβ8+ immune T cells produced markedly greater amounts of IFN-γ than did the Vβ8− population after stimulation with tachyzoite lysate Ags in vitro. Thus, Vβ8+ T cells appear to play a crucial role in the genetic resistance of BALB/c mice against development of TE.