Natural T, γδ, and NK Cells in Mycobacterial,Salmonella,and Human Immunodeficiency Virus Infections

Abstract

NK cells, gammadelta T cell antigen receptor chain-positive cells, and CD3(+)CD16/56(+) (natural T [NT]) cells are involved in innate immunity and immunoregulation; however, their role in clinical infection is not well defined. Cytofluorometric analysis was used to examine peripheral blood from bacteremic, nonbacteremic, and healthy human immunodeficiency virus (HIV)-positive and -negative persons in Malawi, Africa. Mycobacteremia was associated with a higher proportion of CD3(+)CD8(-) gammadelta cells (median, 16.6% vs. 0.7% for all other cells; P<.001), and Salmonella bacteremia was associated with a higher proportion of NT cells (4.3% vs. 2.2%; P=. 002). HIV plasma RNA levels were weakly positively correlated with NT cells (rs=.39; P=.002), NK cells (rs=.38; P=.003), and gammadelta cells (rs=.43; P<.001). Compared with patients who survived, patients who died had a higher percentage of NT cells (3.7% vs. 1. 9%; P=.017) and a higher percentage of NT cells that spontaneously produced interferon-gamma (2.4% vs. 1.2%; P=.035). The data support the clinical relevance of gammadelta and NT cells in mycobacterial, Salmonella, and HIV infections and of NT cells in mortality.

Peripheral Blood Mononuclear Cells Immunophenotyping in Pulmonary Tuberculosis Patients before and after Treatment

“…NKT cells are involved in innate immunity and carry out the recognition of the antigens regardless of αβ T cells (15). In this study, a high percentage of NKT cells were detected in patients before the treatment.…”

Leptospira interrogansActivation of Human Peripheral Blood Mononuclear Cells: Preferential Expansion of TCRγδ+ T Cells vs TCRαβ+ T Cells

“…These results are consistent with previous studies using bovine and human TCR␥␦ T cells that also showed that cytokine production and cell proliferation did not necessarily correlate (80,81). In contrast, activation of TCR␥␦ ϩ T cells by Mycobacterium tuberculosis Ags is dependent upon accessory cells, but is non-MHC restricted (42). However, small phosphoantigens of M. tuberculosis appear to be associated with larger carrier molecules that require processing to allow phosphate ligands to traffic from phagosomes to the cell surface for stable expression and presentation.…”

“…Increased numbers of peripheral blood TCR␥␦ T cells have been documented in a number of different bacterial infections (25,(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55). Our results poise the important question of whether TCR␥␦ ϩ T cells are also elevated in the peripheral blood of leptospirosis patients.…”

“…Not surprisingly, we show that V␥9/V␦2 are expressed by all TCR␥␦ ϩ T cells expanded by Leptospira. Significant increases in the number of peripheral blood V␥9/V␦2 T cells have been documented in humans in many bacterial and parasitic diseases, such as tuberculosis and malaria (23,(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55). In this study we show that patients with acute leptospirosis have increased numbers of peripheral blood TCR␥␦ ϩ T cells.…”

Spontaneous Cytokine Production and Its Effect on Induced Production

“…We ourselves have rarely, if ever, noted spontaneous cytokine production in PBMCs of healthy U.S. blood donors (reference 7 and unpublished data). However, in a multicenter, multiphase study of the immune correlates of bloodstream infections in developing countries (8,10,11), we noticed individuals whose PBMCs produced cytokines without stimulation. Other researchers, measuring either protein or mRNA, have detected spontaneous cytokine production by bronchoalveolar lavage fluid cells of patients with asthma (4), interacting umbilical vein endothelial cells-monocyte cells (17), human milk mononuclear cells (20), peripheral blood lymphocytes of persons with atopic dermatitis (19,23), peripheral blood monocytes of patients with multiple sclerosis (3), or CD4 ϩ T cells of persons with active Mycobacterium tuberculosis pulmonary infection (2).…”