HIV Type 1 Infection Alters Cytokine mRNA Expression in Thymus

We and others have previously shown that HIV infection of human thymus/liver implants in severe combined immunodeficient (SCID-hu Thy/Liv) mice results in a loss of CD4⁺ thymocytes and a decreased recovery of human myeloid and erythroid colony-forming activity. Furthermore, our previous studies have shown that this decrease in colony-forming potential is due to indirect effects, rather than to massive loss of CD34⁺ hematopoietic progenitor cells, suggesting that HIV infection might alter expression of hematopoietic cytokines. Herein we have investigated potential HIV-1-induced perturbations of hematolymphoid microenvironments by determining the effect of HIV-1 infection on levels of cytokine mRNAs in human stroma and thymocytes, using the reverse transcription-polymerase chain reaction (RT-PCR). The levels of interleukin 6 (IL-6), interferon γ (IFN-γ), and IL-2 RNAs increased and macrophage inflammatory protein 1β (MIP-1β) RNA decreased significantly in infected thymocytes. IL-6 RNA levels in stroma also increased somewhat with infection; however, expression of stromal cell-derived factor 1 (SDF-1) by stromal elements was not affected. IL-4 RNA levels were unaffected by infection in both stroma and thymocytes. Antiretroviral drug treatment of the infected animals, which results in restoration of colony-forming potential, tends to restore the cytokine mRNA levels in HIV-1-infected implants to those of mock-infected implants. These results indicate that HIV-1 infection can greatly distort the cytokine profiles in Thy/Liv implants, and suggest that cytokine perturbation could be involved in virus-induced inhibition of hematopoiesis.