The impaired in vitro production of interleukin-2 in HIV infection is negatively correlated to the number of circulating CD4+DR+ T cells and is reversed by allowing T cells to rest in culture: arguments for in vivo CD4+ T cell activation.
In HIV infection, several arguments suggest a certain degree of CD4+ T cell activation which might contribute to lymphocyte dysfunctions. To investigate this possibility, we determined the phenotypes of circulating CD4+ T cells using monoclonal antibodies directed to activation markers and examined whether the defective in vitro interleukin-2 (IL-2) production by purified CD4+ T cells isolated from infected individuals was reversible in rested cultured T cells, a phenomenon suggestive of in vivo CD4+ T cell exhaustion. The number of CD4+ T cells expressing HLA-DR molecules was the same as that observed in controls, remained constant throughout the course of HIV infection, and constituted a major part of circulating CD4+ T cells. In CDC stage II group, the increased percentage of CD4+DR+ T cells was also associated with an increased expression of early activation markers. Defective IL-2 production in vitro was restored when CD4+ T cells were allowed to rest in culture. In addition, the number of circulating CD4+DR+ T cells correlated negatively with the in vitro IL-2 production induced by phytohemagglutinin and phorbol ester by freshly isolated CD4+ T cells. Taken together, these data suggest that in vivo activated CD4+ T cells may participate in the immune abnormalities of HIV infection.
Laboratoire d'Immunologie, Hôpital Charles Nicolle, Rouen, France.
O
O
Lees
S
S
Ramzaoui
D
D
Gilbert
F
F
Borsa
G
G
Humbert
D
D
Leblanc
M
M
Lagarde
F
F
Tron
D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis* / Q000235:genetics; D015658:HIV Infections / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology; D006684:HLA-DR Antigens / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D007700:Kinetics; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D010641:Phenotype; D015375:Receptors, Interleukin-2 / Q000276:immunology; D011990:Receptors, Transferrin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D006684:HLA-DR Antigens; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin