Single cell analysis of IL-4 and IFN-gamma production by T cells from HIV-infected individuals: decreased IFN-gamma in the presence of preserved IL-4 production.
The specific in vitro disturbance of capacities ascribed to Th1 cells in HIV-infected individuals suggests a switch from Th1 to Th2 lymphokine secretion. Indeed, when T cell clones are generated from HIV-infected individuals compared with controls, an increased percentage of Th0 clones is present upon HIV infection. We studied cytokine production in the supernatant of in vitro activated PBMC from a large group of HIV-infected patients at various stages of infection. IL-2, IFN-gamma, IL-4, IL-5, and IL-10 production all were decreased significantly, which does not support a switch to Th2 lymphokine secretion and is possibly due to the generalized impaired response of T cells from HIV-infected individuals to activation signals in vitro. Therefore, we investigated the capacity of single cells to produce a certain cytokine. Intracellular staining of IL-4- and IFN-gamma-producing cells revealed that T cells from HIV-infected individuals contained decreased numbers of IFN-gamma-producing cells, in the presence of normal percentages of cells with the capacity to produce IL-4. This resulted in significantly decreased IFN-gamma/IL-4 ratios in both CD4+ and CD8+ T cells. Thus, in agreement with previous findings in T cell clones, we conclude, from cytokine production upon stimulation of T cells in vitro, that there is a change in the cytokine balance to the Th2 side in HIV infection due to decreased Th1 and preserved Th2 cytokine production.
Meyaard
L
L
Department of Clinical Viro-Immunology, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Hovenkamp
E
E
Keet
I P
IP
Hooibrink
B
B
de Jong
I H
IH
Otto
S A
SA
Miedema
F
F
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002999:Clone Cells / Q000276:immunology; D015331:Cohort Studies; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis*; D015848:Interleukin-5 / Q000096:biosynthesis; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D007376:Interleukin-2; D015848:Interleukin-5; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma