Defective clonogenic potential of CD8+ T lymphocytes in patients with AIDS. Expansion in vivo of a nonclonogenic CD3+CD8+DR+CD25- T cell population.
This study examines the potential mechanism(s) responsible for the defective clonability of CD8+ T lymphocytes in patients with AIDS. By the combined use of one- and two-color fluorescence cytofluorometry we have shown an increase in the number of circulating DR+ cells due to the expression of DR on a relatively large proportion of T lymphocytes (one-third of CD3+ cells), the majority of them belonging to the CD8+ subset. In addition, the majority of CD8+DR+ cells in AIDS patients did not express CD25 Ag (the receptor for IL-2), a surface marker generally expressed on normal activated T lymphocytes. Sorted CD8+DR+ and CD8+DR- cell populations were analyzed comparatively for their ability to proliferate in response to different stimuli, including anti-CD3, anti-CD2, alone or in combination with anti-CD28 mAb and mitogens such as PHA, alone or in combination with PMA. We have demonstrated that CD8+DR+ cells were severely defective in their proliferative response to triggering via these major pathways of T cell activation even when an exogenous source of IL-2 or IL-4 was added to the microcultures 24 h after initiating the cultures. In contrast, CD8+DR- cells showed a significant proliferation in response to the different stimuli and the proliferative response was strongly enhanced by the addition of IL-2 or IL-4. At the end of the stimulation period CD8+DR+ and CD8+DR- proliferating populations were analyzed for CD25 Ag expression. Only 1 to 10% of CD8+DR+ cells expressed CD25 antigen compared with 40 to 50% of CD8+DR- cells. The proliferative defect of CD8+DR+ cells was further confirmed in experiments performed at the clonal level. The analysis of the frequency of proliferating T lymphocyte-precursors in both CD8+DR+ and CD8+DR- subsets showed that the defective clonogenic potential of CD8+ cells in AIDS patients could be in large part ascribed to CD8+DR+ cells. Five percent of CD8+DR+ cells showed a clonogenic potential compared to the 25% of CD8+DR- cells. Finally, we analyzed the surface expression of VLA-2 Ag, a marker of a chronic state of T cell activation, on circulating T lymphocytes. We have shown that a large proportion of CD3+DR+CD25- cells (50 to 80% in the different patients with AIDS analyzed) expressed VLA-2 Ag.(ABSTRACT TRUNCATED AT 400 WORDS)
Pantaleo
G
G
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Koenig
S
S
Baseler
M
M
Lane
H C
HC
Fauci
A S
AS
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015703:Antigens, CD / Q000032:analysis*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D017252:CD3 Complex; D016827:CD8 Antigens; D002455:Cell Division; D002478:Cells, Cultured; D005434:Flow Cytometry; D006679:HIV Seropositivity / Q000276:immunology; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D016029:Receptors, Very Late Antigen / Q000032:analysis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D017252:CD3 Complex; D016827:CD8 Antigens; D006684:HLA-DR Antigens; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D016029:Receptors, Very Late Antigen