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 gamma (IFN-gamma), and IL-2 RNAs increased and macrophage inflammatory protein 1beta (MIP-1beta) 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.
Koka
Prasad S
PS
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine and UCLA AIDS Institute, University of California, Los Angeles, Los Angeles, California 90095-1735, USA. pkoka@ucla.edu
Brooks
David G
DG
Razai
Ali
A
Kitchen
Christina M
CM
Zack
Jerome A
JA
D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1; D006801:Humans; D008099:Liver / Q000821:virology; D016031:Liver Transplantation; D051379:Mice; D016513:Mice, SCID; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000276:immunology / Q000473:pathology / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology / Q000637:transplantation / Q000821:virology; D019562:Viral Load
D016207:Cytokines; D012333:RNA, Messenger