Study of CD4+CD8+ Double positive T‐lymphocyte phenotype and function in Indian patients infected with HIV‐1

Abstract

CD4+CD8+ double positive T cells represent a minor peripheral blood lymphocyte population. CD4+ expression on CD8+ T cells is induced following cellular activation, and as chronic HIV‐1 infection is associated with generalized immune activation, double positive T cells studies have become necessary to understand the immunopathology of human immunodeficiency virus (HIV). The frequency of double positive T cells in persons infected with HIV was studied in comparison to uninfected controls. Further, the expression of CD38, HLA‐DR, and programmed death (PD)‐1 on these cells were ascertained. HIV‐1 specific double positive T cells were also studied for their cytokine secretory ability and phenotype. A significantly higher double positive cell population was observed in the patients with advanced HIV disease (CD4+ T cell counts below 200 cells/µl), as compared to patients with CD4+ T cell counts above 500 cells/µl. Double positive T cells from patients with symptomatic HIV disease had a significantly increased activation and exhaustion levels, compared to asymptomatic subjects and to single positive T cells from the same subjects. HIV‐1 specific double positive T cells showed further increase in CD38 and PD‐1 expression levels. The proportion of CD38 and PD‐1 expressing total and HIV‐1 specific double positive T cells correlated positively with HIV‐1 plasma viremia and negatively with CD4+ T cell counts. HIV infection results in a marked increase of double positive T cell population, and this cell population shows higher level of activation and exhaustion (increased PD‐1 expression) compared to the single positive CD4+ and CD8+ T cells. J. Med. Virol. 84:845–856, 2012. © 2012 Wiley Periodicals, Inc.

Determination of lymphocyte subset reference ranges in peripheral blood of healthy adults by a dual-platform flow cytometry method

“…Moreover, results showed that TCR ␥␦+ values can be obtained using the double-negative CD3+CD4−CD8− phenotype. The CD4/CD8 ratio obtained in this study was comparable with values reported by other studies [4,9,11,12,14,16,17,[20][21][22]30]. However, when gender was evaluated, some studies [11,12,17,21,22] found a higher ratio among females, while others [4,7,9,14,16,32], including this study, did not find differences between genders.…”

“…Chauhan et al [30] observed that the range for their uninfected control group (n = 10) was 0.1-1.2%. However, in this study, the calculated range for healthy adults was wider, probably because a larger number of persons were evaluated.…”

“…Double-positive T CD4+CD8+ cells were a poorly characterized population of effector T cells and can be found in peripheral blood at low frequencies [30,31]. Chauhan et al [30] observed that the range for their uninfected control group (n = 10) was 0.1-1.2%.…”

Circulating CD4+CD28null and extra-thymic CD4+CD8+ double positive T cells are independently associated with disease damage in systemic lupus erythematosus patients

“…20 Furthermore, both cell populations behave similarly in ACPAþ RA patients, 8 and in patients with chronic infections like HIV; 17 moreover, it has been proposed that CD4þCD8þ DP T cells could originate from CD4þCD28null. 21 CD4þCD8þ DP T cells have a pro-inflammatory phenotype, including the production of pro-inflammatory cytokines like IFN-g, 8,[8][9][10][11][12][13][14][15][16][17][18][19][20][21] This subpopulation is associated with a higher level of TNF-a. 22 CD4þCD8þ DP T cells express CD56 and perforin, suggesting they have a cytotoxic capacity.…”

A novel in vitro model reveals distinctive modulatory roles of Plasmodium falciparum and Plasmodium vivax on naïve cell-mediated immunity

“…The double-positive developmental stage of T lymphocytes (CD3 + CD4 + CD8 + ) was elevated upon exposure to cell lysates of P. falciparum . This phenomenon could be associated with the severity of malaria as has been reported for several other infectious diseases, such as HIV [26] and Chagas disease [27], including autoimmune diseases [28] suggesting an immune suppressive role of this cell type [29]. On the other hand, the increment of double-negative developmental stage of T lymphocytes (CD3 + CD4 − CD8 − ) when activated with cell lysates of the P. vivax malaria parasite, emphasized the difference in the response of newly produced immune cells to the two parasites.…”