Lymph Node Natural Killer Research Articles

Triphasic production of IFNγ by innate and adaptive lymphocytes following influenza A virus infection.

Interferon gamma (IFNγ) is a potent antiviral cytokine that can be produced by many innate and adaptive immune cells during infection. Currently, our understanding of which cells produce IFNγ and where they are located at different stages of an infection is limited. We have used reporter mice to investigate in vivo expression of Ifnγ mRNA in the lung and secondary lymphoid organs during and following influenza A virus (IAV) infection. We observed a triphasic production of Ifnγ expression. Unconventional T cells and innate lymphoid cells, particularly NK cells, were the dominant producers of early Ifnγ, while CD4 and CD8 T cells were the main producers by day 10 post-infection. Following viral clearance, some memory CD4 and CD8 T cells continued to express Ifnγ in the lungs and draining lymph node. Interestingly, Ifnγ production by lymph node natural killer (NK), NKT, and innate lymphoid type 1 cells also continued to be above naïve levels, suggesting memory-like phenotypes for these cells. Analysis of the localization of Ifnγ+ memory CD4 and CD8 T cells demonstrated that cytokine+ T cells were located near airways and in the lung parenchyma. Following a second IAV challenge, lung IAV-specific CD8 T cells rapidly increased their expression of Ifnγ while CD4 T cells in the draining lymph node increased their Ifnγ response. Together, these data suggest that Ifnγ production fluctuates based on cellular source and location, both of which could impact subsequent immune responses.

Effect of cocoa-enriched diets on lymphocytes involved in adjuvant arthritis in rats

Cocoa and its flavonoids have potential anti-inflammatory properties in vitro and in acute inflammation models in vivo. The aim of the present study was to ascertain the effects of two cocoa-enriched diets on adjuvant arthritis (AA) in rats, considering not only clinical and biochemical inflammatory indices, but also antibody response and lymphocyte composition. Female Wistar rats were fed with a 5 or 10 % cocoa-enriched diet beginning 2 weeks before arthritis induction and until the end of the study. AA was induced by an intradermal injection of heat-killed Mycobacterium butyricum suspension. The hind-paw swelling (plethysmometry), serum anti-mycobacterial antibody concentration (ELISA), blood and inguinal lymph node lymphocyte subset percentage (flow cytometry), and IL-2, interferon γ and PGE₂ released from splenocytes (ELISA) were assessed. Although the cocoa diets had no significant effect on hind-paw swelling, a tendency to reduce it was observed at the end of the study. Cocoa-enriched diets were able to decrease the serum anti-mycobacterial antibody concentration and the splenocyte PGE2 production, as well as the proportion of T-helper (Th) lymphocytes in blood and regional lymph nodes, which probably includes cells responsible for the arthritic process. The cocoa diets prevented a decrease in the proportion of regulatory T-cells in blood and a disequilibrium between inguinal lymph node natural killer (NK) CD8⁺ and NK CD8⁻ subsets. In conclusion, the cocoa-enriched diets during AA were not able to significantly decrease joint inflammation but modified Th-cell proportions and prevented specific antibody synthesis.

Age-dependent effect of pituitary transplants on immune responses in rat submaxillary lymph nodes: modulatory effect of the autonomic nervous system.

An anterior pituitary was grafted into the breast muscles of male rats on day 5, or under the kidney capsule on day 30 or 60 of life. At the 70th day of life (rats operated at the 5th or 30th day) or at the 100th day of life (rats operated at the 60th day), rats were injected subcutaneously with Freund's complete adjuvant, being killed 2 days later. Rats pituitary-grafted at the 30th day showed a greater hyperprolactinemia than rats grafted at the 5th or 60th day. Submaxillary lymph node natural killer (NK) activity decreased in neonatally pituitary-grafted rats and increased in rats grafted at the 30th or 60th day of life, while lymph node cellularity decreased in rats grafted at the 30th or 60th day. In the case of lipopolysaccharide (LPS)-and concanavalin A (Con A)-induced cell proliferation in lymph nodes, the only significant factor detected was age of transplantation, the effect being less evident in older animals. To examine whether the autonomic denervation of submaxillary lymph nodes affected immune responses in pituitary-grafted rats, animals were subjected to a unilateral superior cervical ganglionectomy (Gx) and/or a parasympathetic decentralization (Dc; by chorda tympani section), 10 days before immunization with Freund's adjuvant. A unilateral Gx blunted the stimulation of lymph node NK activity in rats receiving a pituitary transplant at the 30th or 60th day, but not at the 5th day. Only in sympathetically denervated lymph nodes a significant effect of pituitary transplants on LPS mitogenic effect was found, with significantly less effect of LPS in rats pituitary-grafted at the 5th or 30th day of life. Regarding Con A, a unilateral Gx or unilateral Gx plus Dc uncovered a significant depressive effect of pituitary transplants with a significantly smaller Con A mitogenic effect at each studied age in ipsilaterally Gx lymph nodes, and at 30 and 60 days of age in ipsilaterally Gx plus Dc lymph nodes. Pituitary grafts augmented Con A- induced proliferation in submaxillary lymph nodes at the 5th day of life while they decreased it at the 60th day of life. Pituitary transplants augmented cellularity at the sympathetically denervated lymph nodes and decreased it at the contralateral sham-operated side. Pituitary transplants also diminished lymph node cellularity at the Dc side, the effect being significant in rats transplanted at the 30th day of life. The results are compatible with age-dependent, inhibitory as well as promoting activities of hyperprolactinemia on immune responses in submaxillary lymph nodes, depending in part on intact autonomic nerves.

Murine Lymph Node Natural Killer Cells: Regulatory Mechanisms of Activation or Suppression23

The kinetics and organ distribution patterns of lymph node natural killer (NK) cell activation or suppression were found to vary according to the type, dose, and route of administration of Corynebacterium parvum or polyinosinic-polycytidylic acid (poly I . poly C). Activation of lymph node NK cells by local injections of C. parvum into the footpad or the peritoneum was restricted to the regional lymph nodes; contralateral and distant lymph nodes were not involved. This selectivity persisted even though splenic and peripheral blood NK cells were strongly activated by the same treatment. Conversely, poly I . poly C induced systemic activation of NK cells without selectively activating the regional lymph nodes. The decline of NK cell activity observed 2 weeks after C. parvum treatment was associated with a state of unresponsiveness to a second injection of NK cell stimulants. The expression of C. parvum-induced suppression could be systemic or restricted to the regional lymph nodes. Possible mechanisms for the anatomical compartmentaliztion of NK cell activation or suppression and the implications for the control of tumor growth and dissemination in vivo are discussed.