65   Interleukin-12 (IL-12) Augmentation of T-Cell Proliferation of HIV⁺PBMC Is Mediated via IL-12 Receptor Upregulation.

E. M. Benson, M. L. Jones, R. Puls, J. M. Young, and Q. R. Huang.
Westmead Hosp./Sydney Univ., Australia.

Background:A number of studies have demonstrated that recombinant human (rh) IL-12 augments antigen- specific T-cell proliferation and cytokine secretion by PBMC from patients with HIV infection. Our own data in this regard suggest that the augmentation of proliferation of PBMC from HIV⁺individuals might be greater than that seen using PBMC from HIV^-individuals.

Methods:We hypothesised that the augmented responsiveness of PBMC from HIV⁺individuals may have arisen because of altered IL-12 receptor (IL-12R) expression. In order to address this question, we examined IL- 12R b1 and b2 chain expression on PBMC from HIV⁺and HIV^-individuals.

Results:In the resting state, IL-12R b1 and b2 protein was not detectable on the surface of HIV⁺or HIV^-PBMC using flow cytometric assessment. However, RT PCR measurement of the level of message for IL-12R b1 and b2 showed that both b1 and b2 message was reduced in HIV⁺PBMC compared with normal controls. After mitogen stimulation in vitro, expression of both b1 and b2 protein was detectable on the HIV⁺and HIV^-PBMC using flow cytometry. However, the HIV⁺PBMC increased IL-12R b1 expression with IL-12 coculture whereas the HIV^-PBMC did not.

Conclusions:These results suggest that part of the immune suppression seen in individuals with HIV infection arises from downregulated IL-12R expression and that this defect can be corrected with exogenous rh IL-12.