Rapid and selective depletion of CD4+ T lymphocytes and preferential loss of memory cells on interaction of mononuclear cells with HIV-1 glycoprotein-expressing cells.
Contact of HIV glycoprotein-expressing cells with CD4+ T lymphocytes in vitro causes cell-cell fusion and/or cytopathogenicity. The question of whether this process similarly underlies the death of helper T cells in vivo has not yet been resolved. To investigate the loss of uninfected CD4+ T cells in an environment that may reflect the in vivo situation, unfractionated, unstimulated peripheral blood mononuclear cells were cocultured with HIV-1 glycoprotein-expressing cells, and early alterations of T-cell numbers were quantitated using a newly developed quantitative flow cytometric assay. The results demonstrate that a large fraction of normal-sized, regular CD4+ T cells disappeared immediately on cocultivation with envelope glycoprotein-expressing cells. In contrast, CD8+ T lymphocytes remained unaffected. Significant loss of uninfected T-helper cells required the presence of less than 1% infected cells. Moreover, memory T cells (CD45RO+, CD29 hi+) were depleted more rapidly than naive cells (CD45RO-, CD29 lo+). The observation that a large fraction of intact primary T-helper cells disappeared on contact with HIV glycoprotein-expressing cells suggests that a similar process may occur in vivo and contribute to the loss of T-helper cells in the infected individual. In addition, the preferential loss of memory cells may account for the early loss of immune functions in the course of HIV infection.
Heinkelein
M
M
Institute for Virology and Immunobiology, Julius-Maximilians University, Würzburg, Germany.
Müller
M
M
Kutsch
O
O
Sopper
S
S
Jassoy
C
C
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018920:Coculture Techniques; D005434:Flow Cytometry / Q000379:methods; D015488:HIV Antigens / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D019012:Integrin beta1 / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000821:virology; D008562:Membrane Glycoproteins / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D015488:HIV Antigens; D019012:Integrin beta1; D008562:Membrane Glycoproteins; D017493:Leukocyte Common Antigens