Recombinant HIV-1 glycoprotein 120 induces distinct types of delayed hypersensitivity in persons with or without pre-existing immunologic memory.
Induction of T cell help is critical in HIV-1 control and potentially in prevention by immunization. A practical approach is needed to identify HIV-1-specific helper activities in vivo. We explored the feasibility of measuring delayed-type hypersensitivity (DTH) following intradermal injection of recombinant soluble HIV-1(MN) glycoprotein 120 in HIV-1-infected, vaccinated, and exposed individuals. DTH reactions were elicited within 48 h in 16 of 29 untreated, infected patients and in 24 of 30 uninfected vaccinees. Concomitant envelope-specific lymphoproliferation in vitro was undetectable among 9 infected patients tested with positive envelope-specific DTH. By contrast, no 48-h DTH reactions occurred among 25 high risk and 32 low risk, uninfected volunteers. However, 7--12 days after injection, 10 (40%) high risk and 11 (34%) low risk individuals developed induration resembling DTH, and the cellular infiltrates contained monocytes and T cells. Five of 18 examined also developed anti-gp120 Abs. The very delayed time course and lack of correlation with previous Ag exposure clearly distinguish this reaction from DTH. Thus, HIV-1 skin testing can identify persons with HIV-specific recall responses resulting from infection, in the absence of in vitro lymphoproliferation, and from vaccination. In contrast, very late reactivities may signify chemotactic properties of the envelope protein and/or herald the induction of primary HIV-specific Th1-type immunity.
Hladik
F
F
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Bender
S
S
Akridge
R E
RE
Hu
Y X
YX
Galloway
C
C
Francis
D
D
McElrath
M J
MJ
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology; D016466:CHO Cells; D002175:Candida / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D006224:Cricetinae; D015483:HIV Antibodies / Q000096:biosynthesis / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000821:virology; D007115:Immunization Schedule; D007156:Immunologic Memory / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D007271:Injections, Intradermal; D008213:Lymphocyte Activation / Q000276:immunology; D010865:Pilot Projects; D021382:Protein Sorting Signals / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology*; D018139:Simplexvirus / Q000235:genetics / Q000276:immunology; D012882:Skin Tests
D016915:AIDS Vaccines; D000946:Antigens, Fungal; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C082068:HIV-1 IIIB gp120 subunit vaccine; D021382:Protein Sorting Signals; D011994:Recombinant Proteins