Increased cytolytic T lymphocyte activity and decreased B7 responsiveness are associated with CD28 down-regulation on CD8+ T cells from HIV-infected subjects.
The CD28 receptor on CD4+ and CD8+ T cells interacts with B7 molecules on antigen-presenting cells (APC) to generate essential costimulatory signals. The cytolytic potential of CD8+ T cells could be linked to CD28 expression. Since HIV induces dysfunction of both CD4+ and CD8+ T cells, we evaluated CD28 expression and function in both subsets during HIV infection. CD28 expression on CD8+ T cells from HIV+ subjects was strongly reduced in a disease stage-related fashion. CD28- CD8+ T cells preferentially expressed CD57 and CD11b, but lacked CD26 and IL-2R alpha. The CD8+ T cells from the patients showed a significantly reduced proliferative response to co-stimulation with cell-bound anti-CD3 and B7. Nevertheless, when stimulated with plate-fixed anti-CD3, CD8+ T cells from HIV-infected subjects proliferated normally, and normal levels of IL-2R alpha and transferrin-receptor could be induced on CD28- CD8+ T cells from the patients. In addition, stimulation with plate-fixed anti-CD3 induced proliferative responses in highly purified CD28- CD8+ T cells from both HIV- and HIV+ persons. Furthermore, the increased cytotoxic activity of peripheral blood mononuclear cells (PBMC) from HIV+ subjects, measured in an anti-CD3 redirected assay, was predominantly exerted by CD28- CD57+ T cells. CD4+ T cells from the patients showed a slight but significant CD28 down-regulation and were slightly hyporesponsive to B7 co-stimulation. Decrease of CD28 on CD8+ T cells from HIV+ subjects is associated with an impaired response to co-stimulation via B7. CD28- CD8+ T cells from seropositives, however, are not completely inert, since they contain in vivo activated CTL and they can be additionally activated through a B7-independent stimulation.
Vingerhoets
J H
JH
Department of Infection and Immunity, Institute of Tropical Medicine, Antwerp, Belgium.
Vanham
G L
GL
Kestens
L L
LL
Penne
G G
GG
Colebunders
R L
RL
Vandenbruaene
M J
MJ
Goeman
J
J
Gigase
P L
PL
De Boer
M
M
Ceuppens
J L
JL
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D018122:B7-1 Antigen / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology*; D018959:CD57 Antigens; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D016130:Immunophenotyping; D008024:Ligands; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D018106:CD28 Antigens; D018959:CD57 Antigens; D008024:Ligands; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin