Human interleukin-12 enhances interferon-gamma-producing influenza-specific memory CD8+ cytotoxic T lymphocytes.

Interferon (IFN)-gamma synthesis of CD45RO+ (memory) and CD45RA+ (naive) CD8+ cytotoxic T lymphocytes (CTLs) and the role of interleukin (IL)-12 in the regulation of human CTL functions in virus-specific immunity were investigated. After culture with influenza virus, CD45RO+ CD8+ T cells from human peripheral blood mononuclear cells increased in frequency and exhibited significant major histocompatibility complex class I-mediated CTL activity, whereas CD45RA+ CD8+ T cells did not. Influenza virus-stimulated CD45RO+ CD8+ T cells contained significantly higher levels of IFN-gamma-producing cells and IFN-gamma-specific mRNA than did CD45RA+ CD8+ T cells. Recombinant human IL-12 further enhanced CTL activity and IFN-gamma production by CD45RO+ CD8+ T cells. These data clearly show that human virus-specific CTL activity and coproduction of IFN-gamma are associated with the CD45RO+ CD8+ T cells that are modulated by the cell-mediated, immunity-inducible cytokine IL-12 in humans.

Characterization of T and B cells isolated from mucosa-associated tissues of the rhesus macaque.

This study has assessed T cell subsets according to the expression of CD4 and CD8 and the isotype of surface Ig+ (sIg+) B cells and plasma cells in mononuclear cells (MC) isolated from mucosa-associated tissues of rhesus macaques in comparison to lymphoid cells from systemic tissues, i.e., spleen and peripheral lymph nodes (PLN). Using enzymatic and/or mechanical dissociation methods, mononuclear cells were isolated from lamina propria (LP) of the small (jejunum and ileum) and large (cecum) intestines, parotid glands (PG), and mesenteric lymph nodes (MLN). Approximately equal numbers of CD4+ and CD8+ T cells occurred in mucosa-associated tissues (CD4:CD8 ratios of 0.9-1.2), while slightly higher numbers of CD8+ T cells were seen in spleen and PLN (CD4:CD8 ratios of 0.6-0.9). When the isotypes of sIg+ B cells were assessed in MC isolated from mucosa-associated tissues, the highest frequency of sIgA+ B cells was seen in MLN, which may represent B cells which had recently migrated from IgA inductive sites. However, IgA effector tissues, such as intestinal LP and PG, contained frequencies of sIgA+ B cells lower than those of the MLN. When Ig-producing cells were examined, 50-90% of Ig-secreting cells were of the IgA class. This suggests that sIgA+ B cells differentiate into IgA plasma cells at higher rates in the mucosal effector tissues. Plasma cells of IgM isotype were also found in significant numbers in the LP of the intestine and PG, while IgG plasma cells were most prevalent in spleen and PLN. Taken together, mucosa-associated tissues of rhesus macaques are characterized by higher numbers of CD4+ T cells and Ig-secreting plasma cells of IgA and IgM isotypes than those of systemic lymphoid tissues.

Gingival mononuclear cells from chronic inflammatory periodontal tissues produce interleukin (IL)-5 and IL-6 but not IL-2 and IL-4.

A unique characteristic of the localized inflammatory tissue in the periodontium (e.g., adult periodontitis [AP]) is the accumulation of IgG (IgG1 > IgG2 > IgG3 > or = IgG4) followed by IgA plasma cells (IgA1 > IgA2). However, the exact molecular mechanisms contributing to these elevated B-cell responses at the local disease site are still unknown. Thus, this study has examined the production of cytokines of importance in B-cell responses, e.g., interleukin (IL)-2, IL-4, IL-5, and IL-6 by gingival mononuclear cells (GMC) isolated from patients in severe stages of AP. These cytokines were assessed at the protein and messenger (m)RNA levels to understand their importance for the observed increased B-cell responses present in these tissues. Among the four cytokines tested by respective cytokine-specific, polymerase chain reaction and dot-blot hybridization, high levels of IL-5- and IL-6-specific mRNA were noted in GMC freshly isolated from AP patients. On the other hand, specific message for IL-2 and IL-4 were not present. Further, the analysis of culture supernatants of GMC also revealed that cells from AP patients spontaneously produced IL-5 and IL-6 but not IL-2 and IL-4. In contrast, when peripheral blood mononuclear cells isolated from the same patients were examined for these cytokines, no detectable levels of mRNA or secreted cytokines were noted. These results showed that GMC from localized inflammatory tissues in severe stages of AP possess a distinct cytokine profile represented by high levels of IL-5 and IL-6 mRNA expression and protein synthesis, whereas IL-2 and IL-4 were not detected. Further, this study supports the concept that AP is a localized inflammatory disease, because GMC from the inflamed tissue actively produce IL-5 and IL-6, whereas peripheral blood mononuclear cells from the same patients do not.