Synergistic activation of CD4+ T cells by IL-16 and IL-2.
IL-16, in a CD4-dependent manner, induces high affinity IL-2R (CD25) selectively on CD4+ T cells. Based on this observation, we determined the relative effects of IL-16 on IL-2Ralpha, beta, and gamma expression on CD4+ T cells and of IL-16/IL-2 cotreatment of resting human PBMC obtained from normal individuals on CD4+ T cell proliferation and cytokine production, in vitro. IL-16 increased CD4+ T cell IL-2Ralpha and beta expression, but had no effect on expression of IL-2Rgamma. There was marked synergy of thymidine uptake and expansion of CD4+ T cell numbers in the presence of IL-16 and IL-2 or IL-16 and IL-15 compared with the responses to any of the cytokines alone. By 4 wk, IL-16/IL-2-cotreated PBMC cultures were predominantly CD4+, CD25+ CD45RO T cells. Of the cytokines measured, IL-16 treatment alone was sufficient to induce synthesis of granulocyte-macrophage CSF by 2 wk. IL-16/IL-2 cotreatment did not appear to induce selective proliferation of any Th subset, as cytokines of both Th1 (e.g., IFN-gamma) and Th2 (e.g., IL-5) types were synthesized by the expanded cell populations at 2 and 4 wk. These results suggest that IL-16 can prime CD4+ T cells for IL-2 responsiveness, and therefore may be a useful adjunct to IL-2 therapy for immune reconstitution in disease or therapeutic conditions resulting in CD4+ T cell depletion.
Parada
N A
NA
Pulmonary Center, Evans Memorial Department of Medicine, Boston University School of Medicine, MA 02118, USA.
Center
D M
DM
Kornfeld
H
H
Rodriguez
W L
WL
Cook
J
J
Vallen
M
M
Cruikshank
W W
WW
D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D004357:Drug Synergism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D019410:Interleukin-16 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000502:physiology; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology
D019410:Interleukin-16; D007376:Interleukin-2; D015848:Interleukin-5; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor