Autoantibodies against CD4 cells are associated with CD4 helper defects in human immunodeficiency virus-infected patients

Abstract

To investigate whether autoantibodies against CD4-positive lymphocytes might induce helper dysfunction, autoantibody formation and T-cell function was examined simultaneously in 61 hemophilia patients. Twenty patients were human immunodeficiency virus (HIV)-negative, 26 HIV- positive stage CDC II or III, and 15 were HIV-positive stage CDC IV. T lymphocytes, CD4-positive, or CD8-positive T subsets were cocultured with B lymphocytes and pokeweed mitogen (PWM) for 6 days and Ig- secreting cells were assessed in a reverse hemolytic plaque assay. The presence of IgM, IgG, C3d, or gp120 on the surface of T cells or T subsets was analyzed by flow cytometry. Autoantibodies against CD4- positive T cells were not detected in controls or HIV-negative patients, but were common in HIV-positive patients (20 of 41 patients). In patients with autoantibodies we found an increased incidence of CD4 helper defects (P less than .0001 in CDC II or III patients; P less than .02 in CDC IV patients). 12 of 13 patients with IgM autoantibodies and 4 of 4 with IgG autoantibodies showed CD4 helper defects. Complement fixation had no relevance. Autoantibody formation against CD4 cells was not due to increased in vivo B-cell stimulation (spontaneous plaque formation: 611 +/- 204 PFC/10(6) B cells in autoantibody-negative patients v 650 +/- 202 PFC/10(6) B cells in autoantibody-positive patients; not significant). Thus, our results suggest that autoantibody formation is not caused by a general state of in vivo B-cell activation. Rather, the production of autoantibodies appears to coincide with defects in B-cell proliferation or differentiation, as shown by reduced mitogen-stimulated B-cell responses in CDC II and III patients (P less than .05). Autoantibodies against CD4 cells appear to be involved in the pathogenesis of CD4 helper defects of HIV-infected patients.

Association of T cell dysfunction with the presence of IgG autoantibodies on CD4+ lymphocytes in haemophilia patients; results of a 10-year study

“…Interestingly, CD8 + lymphocytes decrease in association with the immune complex load of CD4 + lymphocytes ( Table 1). The decreased helper cell function of CD4 + lymphocytes for CD8 + cells seems to have an overall suppressive effect on CD8 + cells, similar to that noted previously for B lymphocytes [12]. The impaired helper function of CD4 + lymphocytes thus appears to reduce the proliferation of anti-viral CD8 + lymphocytes.…”

“…HIV infection is characterized by a progressive dysfunction and depletion of CD4 + lymphocytes [1]. During the course of HIV disease autoantibodies against CD4 + lymphocytes are formed and gp120-IgG/IgM-complement complexes are detectable on circulating CD4 + lymphocytes during late stages of the disease [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Recently, we reported that gp120-containing immune complexes on CD4 + lymphocytes are associated with both dysfunction and depletion of CD4 + blood lymphocytes [13][14][15].…”

ATG induction therapy: long-term effects on Th1 but not on Th2 responses

“…Cell separations were performed as described previously [22][23][24]. Briefly, PBMC were separated into 'whole' T and non-T cells (termed B cells in the following) by the rosetting technique.…”

B‐Cell Activation by Superstimaulatory Influenza Virus Hemagglutinin: A Pathogenesis for Autoimmunity?

“…the production of autoantibodies in human immunodeficiency virus (HIV) infection. In HIV-infected patients, a large spectrum of autoantibodies is found, reflecting a specific stimulation of B cells (Weimer et al 1991, Susal et al 1992, Kouri et al 1992, Ditzel et al 1994. It has been demonstrated that the outer envelope glycoprotein of HIV-l gpl20 behaves as a B-cell superantigen, since it binds to 4-6% of B cells belonging to the VH3 family (Berberian et al 1993).…”