Interleukin-12 enhances antigen-specific proliferation of peripheral blood mononuclear cells from HIV-positive and negative donors in response to Mycobacterium avium.
OBJECTIVE
To determine if the addition of recombinant (r) human interleukin (IL)-12 enhances in vitro proliferative responses to Mycobacterium avium of peripheral blood mononuclear cells (PBMC) from HIV-positive donors with CD4 cell counts < 100 x 10(6)/l.


METHODS
PBMC proliferative responses to virulent and avirulent serovars of M. avium in the presence and absence of exogenously added IL-12 were determined in 24 HIV-positive and 11 HIV-negative donors by 3H-thymidine uptake assay. Changes in CD4 and CD8 cell populations after IL-12 treatment and M. avium stimulation were analyzed by FACS.


RESULTS
IL-12 significantly enhanced proliferation of PBMC to both virulent and avirulent M. avium from all 24 HIV-positive donors (P = 0.0001) although the magnitude varied for each donor. In contrast, addition of IL-12 to PBMC from HIV-negative donors only increased the proliferative responses to the virulent M. avium serovar 4 (P = 0.0044). PBMC from HIV-positive donors in the presence of IL-12 responded better to the avirulent serovar of M. avium than the virulent serovar 4. Proliferative responses of HIV-positive donors to M. avium alone, however, were significantly less (P = 0.0013) than that of HIV-negative donors. Increased proliferative responses of HIV-positive donors were independent of CD4 counts. No significant changes in the ratio of CD4+ to CD8+ T cells occurred in either HIV-positive or negative donors under any culture conditions.


CONCLUSIONS
In vitro proliferative responses of PBMC from HIV-positive donors to M. avium were significantly enhanced by the addition of human rIL-12, which was not dependent on their CD4 cell counts. The use of IL-12 as an enhancer of cell-mediated immunity in AIDS patients against M. avium infections deserves further study.
Newman
G W
GW
Department of Rheumatology/Immunology, Brigham & Women's Hospital/Harvard Medical School, Boston 02115.
Guarnaccia
J R
JR
Vance
E A
EA
Wu
J Y
JY
Remold
H G
HG
Kazanjian
P H
PH
D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D018023:HIV Seronegativity / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D009162:Mycobacterium avium / Q000276:immunology* / Q000472:pathogenicity; D012044:Regression Analysis; D014774:Virulence
D018664:Interleukin-12