Patients with type 2 diabetes (T2D) have disease-associated changes in B-cell function, but the role these changes play in disease pathogenesis is not well established. Data herein show B cells from obese mice produce a proinflammatory cytokine profile compared with B cells from lean mice. Complementary in vivo studies show that obese B cell–null mice have decreased systemic inflammation, inflammatory B- and T-cell cytokines, adipose tissue inflammation, and insulin resistance (IR) compared with obese WT mice. Reduced inflammation in obese/insulin resistant B cell–null mice associates with an increased percentage of anti-inflammatory regulatory T cells (Tregs). This increase contrasts with the sharply decreased percentage of Tregs in obese compared with lean WT mice and suggests that B cells may be critical regulators of T-cell functions previously shown to play important roles in IR. We demonstrate that B cells from T2D (but not non-T2D) subjects support proinflammatory T-cell function in obesity/T2D through contact-dependent mechanisms. In contrast, human monocytes increase proinflammatory T-cell cytokines in both T2D and non-T2D analyses. These data support the conclusion that B cells are critical regulators of inflammation in T2D due to their direct ability to promote proinflammatory T-cell function and secrete a proinflammatory cytokine profile. Thus, B cells are potential therapeutic targets for T2D.

The lack of natural killer (NK) cell–specific markers, as well as the overlap among several common surface antigens and functional properties, has obscured the delineation between NK cells and dendritic cells. Here, novel subsets of peripheral blood CD3/14/19neg NK cells and monocyte/dendritic cell (DC)–like cells were identified on the basis of CD7 and CD4 expression. Coexpression of CD7 and CD56 differentiates NK cells from CD56+ monocyte/DC-like cells, which lack CD7. In contrast to CD7+CD56+ NK cells, CD7negCD56+ cells lack expression of NK cell–associated markers, but share commonalities in their expression of various monocyte/DC-associated markers. Using CD7, we observed approximately 60% of CD4+CD56+ cells were CD7neg cells, indicating the actual frequency of activated CD4+ NK cells is much lower in the blood than previously recognized. Functionally, only CD7+ NK cells secrete gamma interferon (IFNγ) and degranulate after interleukin-12 (IL-12) plus IL-18 or K562 target cell stimulation. Furthermore, using CD7 to separate CD56+ NK cells and CD56+ myeloid cells, we demonstrate that unlike resting CD7+CD56+ NK cells, the CD7negCD56+ myeloid cells stimulate a potent allogeneic response. Our data indicate that CD7 and CD56 coexpression discriminates NK cells from CD7negCD56+ monocyte/DC-like cells, thereby improving our ability to study the intricacies of NK-cell subset phenotypes and functions in vivo.

IL-17 is proinflammatory cytokine secreted by a unique CD4+ T (Th₁₇) cell subset and proposed to play a role in host defense. We hypothesized that Th₁₇ cells are lost in HIV-1 infection. HIV-1-infected children with plasma viremia below 50 copies/ml had IL-17 production, whereas those with detectable viremia had minimal secretion. These results imply viral-mediated destruction or impairment of Th₁₇ cells and argue for complete suppression of viremia for reconstitution of Th₁₇ cells.

Mycobacterium tuberculosis (MTB) is a leading cause of mortality worldwide from an infectious agent. Natural killer T (NKT) cells recognize mycobacterial antigens and contribute to anti-MTB immunity in mouse models. NKT cells were measured in subjects with pulmonary tuberculosis, MTB-exposed individuals, and healthy controls. NKT cell levels are selectively lower in peripheral blood mononuclear cells from individuals with pulmonary tuberculosis than in both MTB-exposed subjects and healthy control subjects. This apparent loss of NKT cells from the peripheral blood is sustained during the 6 months after the initiation of MTB treatment. These findings indicate that NKT cells may be an important component of antituberculosis immunity.