Cutaneous response to recombinant interleukin 2 in human immunodeficiency virus 1-seropositive individuals.
We report that 11 human immunodeficiency virus 1 (HIV-1)-seropositive patients, including three AIDS patients, were able to generate a cellular immune response to the intradermal injection of low doses (2-10 micrograms) of recombinant interleukin 2 (rIL-2). A dose-dependent zone of induration appeared at the site of injection, peaked at 24 hr, and was accompanied by the local accumulation of T cells, monocytes, and Langerhans cells. Despite the reductions in the CD4+ T-cell counts in the peripheral blood of most patients, CD4+ T-cells could still be mobilized with rIL-2 injections into the skin. The total number of immigrant cells was equivalent to those in HIV-1-seronegative patients, although the CD4+/CD8+ ratio of the dermal population was reduced. In response to rIL-2, major histocompatibility complex (MHC) class II antigen was expressed on the surface of keratinocytes, Langerhans cells, lymphocytes, and macrophages. In addition, the gamma interferon (IFN-gamma)-induced protein IP-10 rapidly appeared in dermal inflammatory cells and keratinocytes. A majority of HIV-1-seropositive patients demonstrated low or absent responses to common skin-test antigens. Those with positive zones of induration were often defective in the cellular expression of the IFN-gamma-induced MHC class II antigen. The simultaneous administration of rIL-2 and soluble antigen at widely separated cutaneous sites led to an enhancement of skin-test antigen reactivity in seropositive patients. The results suggest that local administration of rIL-2 to seropositive patients may act systemically, stimulating cellular immunity to recall antigens, and thus may be of potential benefit in the defense against opportunistic pathogens encountered in HIV-1 infection.
McElrath
M J
MJ
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021.
Kaplan
G
G
Burkhardt
R A
RA
Cohn
Z A
ZA
D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001706:Biopsy; D017252:CD3 Complex; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens; D004890:Erythema; D006679:HIV Seropositivity; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D012882:Skin Tests; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D007371:Interferon-gamma