HIV-induced immunodeficiency. Relatively preserved phytohemagglutinin as opposed to decreased pokeweed mitogen responses may be due to possibly preserved responses via CD2/phytohemagglutinin pathway.
We studied the proliferative response of PBL to the mitogens PHA and PWM and Candida albicans Ag in 301 HIV seropositive homosexual men, of whom 55 had AIDS. The responses to PHA were reduced only in the clinically ill HIV seropositive subjects. In contrast, the responses to PWM were profoundly reduced in most HIV seropositive subjects including the asymptomatic group. Further analysis of 16 HIV seropositive subjects showed that the proliferative responses were reduced in both CD4 and CD8 T cell subsets. A total of 15 HIV seropositive individuals with low responses to PWM, of whom seven had AIDS and eight controls were chosen for the following studies. Expression of T3, Ti, delta receptors, and CD2 was investigated and showed an increased percentage of CD2 receptors positive cells in HIV seropositive subjects without AIDS. The proliferative responses of PBL to stimulation with PHA, PWM, antibodies to CD3, or antibodies to CD2 were investigated and showed significant correlation in controls, whereas in contrast, only the responses to PHA and CD2ab correlated in patients with AIDS. The proliferative responses to CD2ab and CD3ab in controls were larger than the responses to both PHA and PWM. In patients, these responses were less suppressed than the responses to PWM indicating that stimulation with mitogens is more complex than a simple stimulation of Ti/T3 and CD2 receptors. Further investigations were done on resting T cells, i.e., lymphocytes depleted of macrophages and pre-activated cells. Addition of PHA to these cells resulted in preactivation with expression of IL-2R (CD25) but not in proliferation. In contrast, addition of PHA plus SRBC, which bind to the CD2 receptors caused IL-2R expression, IL-2 production, and proliferation. Addition of PWM + SRBC did not result in proliferation. A comparison of the responses to PHA + SRBC of resting T cells from 26 HIV seropositive individuals, of whom seven had AIDS and 12 seronegative controls, showed that these responses were normal or only slightly decreased in the 19 seropositive men without AIDS whereas it was decreased in AIDS patients. Nevertheless, all AIDS patients showed clear-cut responses in this assay. Thus, the discrepancy between responses to PHA and PWM may be explained by an at least partially preserved function of the PHA/CD2-dependent pathway. We suggest that the defect induced by the HIV infection primarily concerns T3/Ti-induced responses.
Hofmann
B
B
Department of Clinical Immunology, University Hospital, Copenhagen, Denmark.
Jakobsen
K D
KD
Odum
N
N
Dickmeiss
E
E
Platz
P
P
Ryder
L P
LP
Pedersen
C
C
Mathiesen
L
L
Bygbjerg
I B
IB
Faber
V
V
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000276:immunology*; D000946:Antigens, Fungal / Q000276:immunology; D018801:CD2 Antigens; D017252:CD3 Complex; D002176:Candida albicans / Q000276:immunology; D006801:Humans; D007399:Interphase; D008213:Lymphocyte Activation; D008297:Male; D010835:Phytohemagglutinins; D011043:Pokeweed Mitogens; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000276:immunology; D011971:Receptors, Immunologic / Q000032:analysis / Q000276:immunology*; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology / Q000502:physiology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000946:Antigens, Fungal; D018801:CD2 Antigens; D017252:CD3 Complex; D010835:Phytohemagglutinins; D011043:Pokeweed Mitogens; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic